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At the foot of the Scottish Highlands, set in a natural haven for seals, ospreys, deer, wild cats, and migratory pink-footed geese, is an eco-village run by the Findhorn Foundation, a United Nations–affiliated not-for-profit. The spiritual community of more than 500 people believes in “creating a better world by starting with themselves.”
In mid-April, the remote enclave was pulled into the global COVID-19 fight by an unexpected email from an American physician 6000 km across the Atlantic.
At breakfast time on Sunday, March 22, Graham Meltzer, a coworker at the Findhorn Foundation, opened an email from Jeremy Warner, MD, an oncologist at Vanderbilt University, in Nashville, Tennessee. The email asked if the Findhorn Foundation would allow Warner to take over the domain name “ccc19.org” for a new medical project, the COVID-19 and Cancer Consortium (CCC19).
The Findhorn Foundation was using the domain name for a conference called Climate Change and Consciousness 2019, and they no longer needed it, said Graham.
“It took me about 5 seconds to make the decision,” Meltzer said. He decided to pass along the digital assets free of charge. “It was gratifying to know that it was going to a good cause.”
Warner recalled the moment: “I’m incredibly grateful to this organization. They didn’t know anything about us, but just out of the goodness of their hearts they were willing to do this.”
Within days, ccc19.org became the flagship site of the crowdsourced CCC19 registry, now the largest and most comprehensive body of data on the effects of COVID-19 on patients with cancer.
In just 3 months, CCC19 partnered with 110 institutions; garnered 317 collaborators in the United States, Canada, the European Union, Argentina, the United Kingdom, and Brazil; accrued data from 2300 patients; and published its first results in the Lancet. The article provided answers to the key question that has haunted oncologists for months: is it safe to treat cancer during the pandemic?
It may seem self-evident to clinicians that cancer patients, who are immunocompromised by anticancer treatments as well as cancer itself, are in greater peril from COVID-19. However, what the pandemic means for the approximately 18 million people who have cancer in 2020 is unclear. Should treatment for their cancer be postponed until the risk for coronavirus infection recedes? Or should they risk being immunocompromised by the treatment while the virus is still circulating?
It’s “terrifying” what cancer patients are going through, said Corrie Painter, PhD, of the Cancer Program of the Broad Institute of the Massachusetts Institute of Technology and Harvard University, who has had cancer herself. “Patients are making the decision, do I risk my life with cancer treatment and die of COVID, or do I try to prolong my life and give up chemo?” She added, “There’s the fear of the known, fear of the unknown, and the inability to make data-informed decisions.”
The CCC19 initiative aimed to change all that.
CCC19 was born with a call to action on Twitter from Aakash Desai, MD, an internal-medicine resident at the University of Connecticut. On March 13, Desai tweeted: “#COVID19nCancer is important! Data out of China indicates higher risk. Lets [sic] collaborate to survey data, provide update on the effective risk mitigation strategies @NIH designated cancer centers for #oncologists #cancer patients”.
Desai explained in an interview with Medscape Medical News that he was alarmed by the first data from China on the fate of cancer patients who contracted COVID-19. The anxiety-inducing study, which was conducted by Wenhua Liang, MD, and colleagues from China’s National Clinical Research Center for Respiratory Disease, was published in the Lancet on February 14. The study followed 18 cancer patients in a cross-country cohort of 2007 people with confirmed COVID-19. The patients who had undergone chemotherapy or surgery in the past month had a fivefold increased risk for clinically severe events compared to those who had not received treatment in the prior month. As a result, Liang’s team raised the possibility of “intentional postponing” of adjuvant chemotherapy or elective surgery for stable patients in areas where COVID-19 was endemic.
Concerning as it was, the Liang study had few cancer patients and so was far from definitive. Desai said, “I was curious to see where in the US we could collect data to figure this out. Given the fact that [COVID-19] is widespread, it required more than an institutional effort to get that data going.”
Over the next 24 hours, to his surprise, Desai received 15 replies to his tweet from senior physicians supportive of a crowdsourced registry. For a name, he suggested, the COVID-19 and Cancer Consortium (CCC).
“When I tweeted it out, I didn’t imagine that we’d be able to make a difference. Then we got 1000 patients in 75 days,” said Desai.
One of the strengths of social media, Desai said, is that it breaks through medical hierarchies. He said: “For me to reach out to, let’s say, a chief of GU oncology in Dana Farber is difficult without social media.”
Warner, who is the medical director of the Vanderbilt Cancer Registry, was one of the senior oncologists who jumped on the idea. Warner told Medscape Medical News that the idea was very attractive to him and his colleagues: “This came out of an amazing group of individuals, individual physicians primarily, who came together because they wanted to do something about the pandemic, feeling powerless and not sure how to help.”
Over the next 48 hours, emails went back and forth between Desai and Warner as well as other heavy-hitting oncologists, such as Gilberto De Lima Lopes, MD, associate director of global oncology at the University of Miami, Florida, and Nicole Kuderer, MD, of the Advanced Cancer Research Group, in Kirkland, Washington.
By 6:48 PM on March 15, 2 days after the initial tweet, Warner had a beta version of the CCC19 REDCap (Research Electronic Data Capture) database up and running.
Before another 2 days had passed, the CCC19 registry had a green light from the ethical review board and a permanent home at Vanderbilt University Medical Center.
Warner spread the word on Twitter: “Folks – the COVID-19 and Cancer Consortium registry is now LIVE! If you are caring for a cancer patient affected by #COVID19 please consider reporting here: bit.ly/2WsS8Mx. Spread the word!”
Folks – the COVID-19 and Cancer Consortium registry is now LIVE! If you are caring for a cancer patient affected by #COVID19 please consider reporting here: https://t.co/gLo16cHlt7. Spread the word! @ADesaiMD @arkhaki @NicoleKuderer @DrChoueiri @puhfu @gary_lyman @Hem_Onc #CCC19
— Jeremy Warner MD, MS, FAMIA, FASCO (@hemoncwarner) March 17, 2020
One month later, almost 90 institutions had signed up.
Warner commented: “What surprised me was that so many large organizations wanted to participate ― and approached us.” The enthusiasm of top-echelon participants and the urgency of the issue propelled the team over the administrative hurdles. An 11-person steering committee came together within days, followed by subcommittees to manage activities such as publications. Members agreed that it was more important to keep things moving than to become bogged down with formalities, such as a charter, Warner said.
An article describing the methodology used by the CCC19 team was published in Nature Cancer on April 21, with Desai as first author.
The first CCC19 registry data appeared in the Lancet on May 28. For this article, the researchers analyzed data from March 17 to April 16 from 928 patients. The primary endpoint was all-cause mortality within 30 days of a diagnosis of COVID-19.
Cancer was, indeed, associated with a more fearsome course for COVID-19. The team reported that 13% of cancer patients who developed COVID-19 had died. Echoing the Chinese study that was published in February, these data also showed that active cancer conferred a fivefold increased risk for death in comparison with remission (odds ratio, 5.2; 95% confidence interval, 2.77 – 9.77).
However, results from the crowdsourced CCC19 data diverged in several important respects from earlier, smaller studies. For example, race, ethnicity, obesity status, and type of anticancer therapy had no impact on mortality risk among cancer patients who developed COVID-19.
Most significantly, CCC19 shone light on whether oncologists should be treating cancer patients at all during the pandemic. Contrary to findings from the Chinese study, CCC19 found no association between 30-day all-cause mortality and recent cancer treatments such as surgery or chemotherapy.
The authors concluded, “…curative surgical resections, adjuvant chemotherapy, and maintenance chemotherapy should continue during the SARS-CoV-2 pandemic, with extreme caution.” The authors advised that “this finding should not be interpreted as a recommendation,” noting wide regional variation and comorbidity-related risks.
“Crowdsourcing” to Solve a Problem
The term “crowdsourcing” was coined by journalist Jeff Howe in an article published in Wired magazine on June 1, 2006. The methodology has grown exponentially in academia and is generally defined as a large group of people using their individual knowledge to collectively solve a problem. In medicine, crowdsourcing has been harnessed for diagnosis, surveillance, public health, genetics, mental health, drug repurposing, adverse drug reactions, clinical-trial protocols, healthcare management, and other uses.
In crisis medicine, such as COVID-19 response, crowdsourcing fueled by social media is proving to be a powerful tool, vastly increasing the speed with which physicians can find solutions. CCC19 joins a list of 10 other crowdsourced COVID-19 projects, three in oncology: the UK Coronavirus Cancer Monitoring Project, the ASCO Registry, and, in thoracic cancer, TERAVOLT.
Research projects such as CCC19 are also game changers in that they burst the bonds of traditional academic medicine, commented Painter. She joined the steering committee of CCC19 as a patient representative after being recruited “out of the blue” by Warner. “It was a huge signal of how progressive their thinking was; it was not just a token gesture,” she told Medscape Medical News.
Painter said that the CCC19 committees act quickly on advice from patient members. She cited the CCC19 grant-application process, onerous for patient reviewers, many of whom were unwell. Painter suggested requiring a patient-friendly abstract, and the idea was immediately adopted.
Painter rejects the view that patients have no place in complex research and practice-changing endeavors such as CCC19. “Educated patients self-advocate for themselves instead of being passive recipients of care,” she said. “They can ask deeper questions of doctors and hold them accountable for their care.”
The CCC19 Lancet analysis provided an example of accountability in crisis medicine. The authors noted that 270 (30%) of the patients were given hydroxychloroquine, either alone or in combination with azithromycin. Yet only two patients received the drug in the context of a clinical trial, despite pleas in the medical literature to avoid off-label drugs for COVID-19 except in randomized clinical studies.
However, the overwhelming mood of the CCC19 team is celebratory rather than censorious.
Painter commented: “The absolute dedication of Jeremy [Warner] and the rest of the steering committee to go head down and work 24/7 collecting and analyzing the data to get it out to world…. The sense of urgency was unparalleled. It was incredible to be on the inside watching it all come together.”
In Scotland, Graham Meltzer had a spiritual take on the Findhorn Foundation’s contribution to CCC19: “Among our many beliefs and practices, we include manifestation, synchronicity, right timing…so it was actually no surprise that just at the moment that we had relinquished our interest in our domain name, this request came from the Universe to continue its use.”
Warner summed up the collaboration more prosaically: “The short story is that all physicians should join Twitter,” he said.
Desai and Meltzer have disclosed no relevant financial relationships. Warner has received personal fees from Westat and IBM Watson Health and owns stock in HemOnc.org. Painter or an immediate family member currently or during the past 2 years has owned stock or held an ownership interest in Pfizer, Epizyme, Inovio, OPKO Health, and Roche. Liang and colleagues have disclosed no relevant financial relationships.
Lancet Oncol. Published online February 14, 2020. Full text
Nat Cancer. Published online April 21, 2020. Full text
Lancet. Published online May 28, 2020. Full text
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