In early 2020, British oncologist Dr Sheeba Irshad was preparing to start a trial of three new treatments for patients with an aggressive form of breast cancer. Then Covid-19 derailed years of planning.
Only three of the study’s nine prospective sites have since resumed recruitment. The remainder have faced staff shortages as hard-pressed teams in England’s NHS have focused on caring for Covid-19 patients and clearing lengthy waiting lists for non-urgent treatments.
In wealthy nations the health emergency has derailed studies such as Irshad’s, which pave the way for future breakthroughs and can offer a last chance to patients when other treatments have failed. Drops in cancer diagnosis – as screenings were delayed or patients feared seeking care – created a backlog of cases that also made it harder to recruit clinical trial participants.
Irshad said the patients potentially eligible for her study had had their cancers detected early and “had all the treatments that we could offer”. Yet because such “triple negative” tumors tended to be resistant to chemotherapy, they were at high risk of a recurrence.
“To go away from an oncology clinic without having. . . options like these trials is actually quite cruel, ”said Irshad, who is based at Guy’s & St Thomas’ NHS Trust in central London.
Although there have been notable pockets of innovation, experts fear the legacy of disrupted trials may last long after the pandemic fades. Cancer Research UK, one of the field’s biggest funders globally, said around 75 per cent of all new trials sponsored by the charity had opened 40 per cent or fewer sites than originally planned.
One consequence of the slowdown may be a brain drain. A survey of clinical researchers, conducted by the charity, found three in 10 respondents were more likely to leave clinical cancer research within the next five years. They cited increased workloads during the pandemic as a significant factor.
“We need to treat the growing crisis facing clinical research with the same urgency as the pandemic,” said Prof Charles Swanton, chief clinician at Cancer Research UK.
Researchers in mainland Europe have experienced similar frustrations over the past two years. Prof Giuseppe Curigliano, who leads a division specializing in early drug development at the European Institute of Oncology in Milan, said the number of patients enrolled in trials fell by 90 per cent over the course of 2020.
As in the UK, the overriding factor was pressure on the workforce. “During the first [wave of the] pandemic many medical oncologists working in Italy were involved in the management of Covid patients and not cancer patients, ”he said.
Recruitment had returned to 70 per cent of pre-pandemic levels in 2021 and enrollment levels in the first three months of 2022 were identical to those in the first three months of 2019, he said.
But for some patients, the return to normality will have come too late. Curigliano cited a late-stage trial of a new drug, conditionally approved in both the US and Europe, to treat metastatic breast cancer. Owing to pandemic disruption, few patients in Europe had been able to participate in the study.
“So many patients lost the opportunity to benefit from an experimental agent that then became the standard of care,” he said. “The reduction [in recruitment]I believe, also impacted the overall survival of our patients. ”
However, the difficult circumstances have spawned innovation among clinical researchers and big pharma companies in parts of Europe and the US. Dr Josep Tabernero, director of the Vall d’Hebron Institute of Oncology in Barcelona, said oncology drug trials run during its auspices had increased during the pandemic, rising from 570 in 2019 to 655 in 2021.
Tabernero said telemedicine, in which video software is used for remote consultations, was used to screen and monitor patients. Data from trials were also reviewed remotely. As a private foundation, the institute had the resources to hire IT workers and to ensure that staff were not diverted to treat Covid patients, he said.
Pharmaceutical companies also embraced new ways of working to keep studies on track. Charles Fuchs, global head of oncology at Basel-based Roche, said his company changed the way it delivered medicines, from reducing the number of infusions to cut the risk of hospital attendance, to using more local sites so patients did not have to travel as far.
Enrollment in trials declined in 2020 but Roche was able to catch up in 2021 by increasing the number of trial sites and concentrating them in parts of the world where the virus was not as prevalent, he said.
Its Swiss neighbor, Novartis, said it has also managed to keep 95 per cent of its approximately 120 oncology trials on schedule. Jeff Legos, global head of oncology, said the company analyzed data showing areas in which there were Covid outbreaks in order to send trial participants to different facilities.
Amid the challenges, the use of technology has enabled drugmakers to reach a wider range of participants.
However, Samit Hirawat, chief medical officer at drugmaker Bristol-Myers Squibb, warned that disruption may persist despite trial enrollment almost regaining pre-pandemic levels by the end of last year. Some trials in oncology, hematology and cell therapy still lag behind pre-pandemic rates he said.
For Irshad, frustration at the continuing delays in her own trial is magnified by the difference it could make to women who have run out of options. “Being able to hold out some kind of hope to these patients, when you would otherwise have nothing to offer them. . . It’s huge, ”she said.