“Widespread disruption of neuroendovascular trials occurred because of COVID-19,” conclude the investigators of a survey-based study examining the impact of the pandemic. Now, as sites begin to resume clinical research, first author Ansaar T Rai of West Virginia University, Rockefeller Neuroscience Institute (Morgantown, USA), and colleagues throughout the USA call for steps to mitigate similar challenges that may arise in the future.
The study, recently published in the Journal of NeuroInterventional Surgery (JNIS), focused on randomised controlled trials (RCTs) and single-arm studies for acute ischaemic stroke and cerebral aneurysms. The survey was developed by a group of senior neurointerventionalists, subsequently sent to sites identified through the clinical trials website, study sponsors, and physician investigators.
“The survey was sent to 101 institutions, with 65 responding,” state Rai et al, as they added that stroke RCTs were (prior to the pandemic) being conducted at 40 sites, aneurysm RCTs at 22 sites, stroke single-arm studies at 37 sites, and aneurysm single-arm studies at 43 sites.
However, following COVID-19, the authors report that enrolment was suspended at 51 (78%) of sites; completely at 21, and partially at 30 sites. Moreover, missed trial-related clinics, imaging follow-ups, and protocol deviations were reported by 27, 24, and 27 sites, respectively. Negative reimbursements were reported at 17 sites.
The majority of sites, Rai and colleagues note, were forced to put new trials on hold. The team found that many study coordinators (63%) worked from home, and 31% reported a personal financial impact. While remote consent was possible for some studies at 34 sites, only five sites reported that remote consent presented a viable option for all studies underway.
Regarding the sites with suspended trials (51), endovascular treatment without enrolment occurred at 61% of sites for stroke, and 45% of sites for aneurysms. Rai and the team found that this resulted in a total of 277 patients with acute ischaemic stroke, and a further 184 patients with cerebral aneurysms being treated without consideration for trial enrolment.
Discussing the justification for the investigation, the team state that while modifications for emergency treatment and safety procedures to accommodate those with COVID-19 have been widely agreed on and adopted, “the impact of COVID-19 on clinical research efforts have been less clear.
“Disruption of clinical research infrastructure has implications for patient enrolment, study timing, sponsorship, and advances in clinical care and disease understanding. At the time of writing, fears of resurgent or re-emergent disease remain prominent,” add the authors.
“Long-term threat” to stroke research in the UK
The Stroke Association, the leading stroke charity in the UK, has issued a statement announcing that almost three quarters (74%) of its stroke research projects have been suspended in light of the pandemic.
As the charity anticipates a shortfall of £1.5 million in its funding programme this year to resume current research and support vital new projects, it warns of a “catastrophic knock-on effect” for stroke research, which could delay access to treatments.
The Stroke Association explains that despite stroke being a leading cause of adult disability, research remains underfunded in the UK in comparison to strokes devastating effects and other conditions, such as cancer. In 2016, the charity revealed that just £48 is spent on stroke research per patient, compared to £241 on cancer research. This, they argue, has now been compounded by the devastation that COVID-19 has had on the charity’s fundraising capabilities and researchers’ abilities to continue their work.
Findings from a survey conducted by the Stroke Association also reveal the broader impacts that the pandemic has had on stroke researchers in the UK:
- One in five researchers (22%) will need more funding.
- Two-thirds (66%) of researchers have said they need to make changes to their studies for their projects to continue. This could have added cost implications and change what the researchers had initially set out to achieve.
- One in five (18%) research projects had team members redeployed to front line work NHS working, for example as neurologists, physiotherapists and occupational therapists.
Given these data, Rubina Ahmed, research director at the Stroke Association commented in the statement: “Our work has laid the foundations for one of the most successful public health awareness campaigns in England, the Act FAST campaign, which helps people to recognise the signs and symptoms of stroke. We also funded early research into the new emergency stroke treatment, thrombectomy.
“But a lack of funding for research is now a ticking time bomb. If we do not act now the coronavirus pandemic could set back stroke research for years to come. The research community will struggle to get projects back up and running, but it is vital for every stroke survivor and their loved ones that we do.”
Recommendations moving forward
Though respondents of the survey in the USA indicated widespread disruption of neurovascular clinical research, as well as research infrastructure, amid the pandemic, the authors suggest that it reveals opportunities for “increased infrastructural strength and pliability”. This includes the increased use of virtual access for consent and follow-up, as well as the benefits of platform trial design at times when flexibility and responsiveness are key advantages.
“Many questions remain to be answered,” Rai and colleagues speculate. For example, they query how the field will incorporate COVID-19 screening into trial criteria.
The team writes that in the survey, 40% of the responding sites did not have any protocols in place for remote consent. In light of this, they say that study sponsors, local institutional review boards, and federal authorities regulating these trials will have to demonstrate creativity in modernising these procedures.
“Harnessing emerging virtual technologies that allow for face-to-face interactions with legally authorised representatives, electronic exchange of documents, and digital signatures, represents a clear opportunity,” add the authors.
However, Rai and the team conclude that, based on expert predictions of the disease course, “disruptions due to COVID-19 will continue”. They argue that trials conducted in this “restrictive environment” will need to evolve. “Decisions about how to maintain enrolment during the current pandemic and in the event of future similar disruptions must be prioritised.”