A patient-reported symptom tracking method used for patients with cancer has now been adapted for patients with COVID-19. Investigating the effect of famotidine, a potential treatment for COVID-19, on non-hospitalized patients with COVID-19, clinicians at Northwell Health and cancer researchers at Cold Spring Harbor Laboratory (CSHL) developed the method to use in addition to laboratory tests. This outpatient approach addresses the need to care for the majority of COVID-19 patients who do not require hospitalization. The first clinical case series showed that famotidine may help patients with mild to moderately severe symptoms from COVID-19. Next, the team will test the drug in a randomized clinical trial.
Published in the journal GUT, the Northwell-CSHL case series is unique in its adaptation of quantitative tracking of patient-reported outcome measures. The methodology is suitable for testing drugs in patients well enough to be managed at home and allows the recruitment of diverse subjects via community-based health organizations and individual practitioners.
The lead author of the study, CSHL Assistant Professor Tobias Janowitz, is a Medical Oncologist and a Cancer Researcher, who investigates the whole-body causes and effects of diseases. "The experience of a patient at one point in time is very valuable, but learning about the change in their experience over time is even more important," says Janowitz. "Change indicates if the patients' condition is getting better or worse. A graded symptom score enables the physician and the patient to track symptoms using numbers."
Observing that for COVID-19, most symptomatic people do not require hospitalization, Janowitz and colleagues developed a 4-point scale for six common COVID-19 associated symptoms that patients score every day. Janowitz simplifies how the scale can help track the course of a patient's disease:
"You may call up your doctor and say, I have headaches and shortness of breath, and am only able to do the basics for self-care, which would be grade 3 symptoms. If you still had the symptoms two days later, but are now able to do light work, these symptoms would now be scored at grade 2. This approach makes it very easy for you and your doctor to document that your symptoms are improving. The value of this approach from a research perspective is that experiences from many patients become comparable and can be pooled for analysis."
If a drug speeds recovery, then most patients will report more rapid improvement of symptoms.
The innovations in this study are the product of scientists and physicians who never expected to work on a pandemic infection. But the collaborative, multidisciplinary approach is a hallmark of the strategic research affiliation between CSHL and the academic physicians at Northwell Health. Chief, General Internal Medicine, Northwell Health and Professor at the Feinstein Institutes, and a co-author on the study, Joseph Conigliaro says:
"There are a lot of things that we were doing that worked well in how we address this pandemic. I'm a health services addiction researcher. I didn't think I'd ever be the person who would be studying this pandemic and this virus. And Tobias does cancer research. What we did is we used our existing tools and talents that were not specifically geared towards studying a viral pandemic, but we used it and modified it in ways that were very, very helpful."
CSHL Professor David Tuveson, Director of the CSHL Cancer Center and another co-author, is interested in the broader implications of the patient-oriented research approach as a way to better connect science and healthcare. CSHL's commitment to bridging the gap between research and the clinic is evident in an initiative championed by Janowitz to study how disease impacts the entire body. Tuveson says:
"You're trying to scientifically assess a symptom, is what you're really doing. Tobias and his colleagues can look at the whole body while they study cancer. And so Tobias is someone who thinks about the big picture of health. He's basically shifting his approach to solving complex problems to COVID-19 and he started by saying 'how can we describe one patient relative to the next?'"
Janowitz agrees, "It seems reasonable to me to make that extension to this healthcare crisis and to acknowledge that we can learn a lot from the individual who has the disease as long as we find a way to make it quantifiable."
Once validated, the patient-reported symptom tracking method will be a key component in a clinical trial that is "double-blind," meaning that neither patient nor doctor know whether the patient is getting the test drug or a placebo until the trial is completed. Without a double-blind clinical trial and a careful scientific examination of the mechanism of action of a drug and its side effects, it is impossible to rule out that the preliminary findings were due to factors other than the drug. The early findings of this case series were communicated to co-author Dr. Timothy Wang at Columbia University Medical Center. Interestingly, Dr. Wang and colleagues were also able to find an association between famotidine usage and the improved outcomes of patients hospitalized for COVID-19. Based on the findings in the case series, a double-blind clinical trial of famotidine is the next step in the joint plan of the Northwell-CSHL team. Other treatments may also be explored.
Conigliaro explains why he is hopeful that the study will work as designed to find drugs that will be effective against COVID-19:
"We had about a thousand patients that we tracked in our practices, just in my couple of academic practices, that never made it to the hospital. And my Doc's were calling them every day and asking all those questions: 'Do you have aches and pains? Do you have fever today? How's your breathing today?' We didn't know what their blood levels were. We didn't know what their oxygen levels, because we didn't have access to that. So these surrogate measures are very common and the best way to assess what's going on in the outpatient. I'm actually pretty confident. I think there'll be another surge but I think we'll be much better prepared and I think that hopefully lives will be saved."
About Cold Spring Harbor Laboratory
Founded in 1890, Cold Spring Harbor Laboratory has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. Home to eight Nobel Prize winners, the private, not-for-profit Laboratory employs 1,100 people including 600 scientists, students and technicians. For more information, visit http://www.
About the Feinstein Institutes
The Feinstein Institutes for Medical Research is the research arm of Northwell Health, the largest healthcare provider and private employer in New York State. Home to 50 research labs, 2,500 clinical research studies and 5,000 researchers and staff, the Feinstein Institutes raises the standard of medical innovation through its five institutes of behavioral science, bioelectronic medicine, cancer, health innovations and outcomes, and molecular medicine. We make breakthroughs in genetics, oncology, brain research, mental health, autoimmunity, and are the global scientific leader in bioelectronic medicine - a new field of science that has the potential to revolutionize medicine. For more information about how we produce knowledge to cure disease, visit feinstein.northwell.edu.