COVID-19 Trial Insights from the WCG Knowledge Base™
The WCG Trial Insights series brings you weekly insights on trial activity throughout the COVID-19 crisis, powered by the WCG Knowledge Base.
The WCG Trial Insights series brings you weekly insights on trial activity throughout the COVID-19 crisis, powered by the WCG Knowledge Base.
WCG continues to track the progress of global interventional industry-sponsored COVID-19 trials that have been reported as planned/initiated so far this year, now numbering 471. Of those, 34 have been reported as complete, with 15 completing in the past six weeks. To date, six studies have reported meeting their primary endpoint, with another four reporting they did not meet their endpoint. Notably, 137 studies are still planned for initiation in 2020, so this data will continue to reflect additional activity.
In our continuing analysis of the clinical trial landscape and the impact of COVID-19, we’ve looked at the trends of trial starts as compared to trial start means over the past three years, corrected by quarterly variations.
As previously reported in this email series, we’ve seen a significant dip in overall trial starts in 2020. This week, we’re taking a deeper look at the top therapeutic areas associated with the largest number of clinical studies.
In all charts, “0” reflects the mean number of study starts in that quarter in the prior three years.
As seen below, interesting patterns emerge as we evaluate how the surge in infectious disease study activity has surpassed more established trends associated with the top therapeutic area study starts in the past three years.
Oncology and CNS studies appeared somewhat stable prior to COVID-19, but new starts of infectious disease and cardiovascular studies were both trending down before the pandemic.
While oncology study starts declined in 2020 due to the COVID-19 pandemic, it is anticipated that the number of starts will return to levels consistent with 2018-2019 as study starts that were delayed due to COVID-19 ultimately recommence.
CNS studies show a dramatic dip in trial starts this year, as compared to the rolling three year mean.
The number of trial starts in cardiovascular indications was already decreasing prior to the current crisis, but showed the steepest decline in starts in 2020.
We see a dramatic increase of infectious disease trial starts—largely due to COVID-19 trials—during the current pandemic, even though trial starts in this therapeutic area had been steadily decreasing in prior years.
Of the top 100 COVID-19 clinical trial listings attracting the most views on WCG CenterWatch iConnect from June through September, 56% were treatment related and 25% were vaccine trials, representing a slight increase in both trial types since we last reported this data more than a month ago. Vaccines continue to have disproportionately more interest than their percentage share of total listings, which continues to reflect public interest in vaccine development.
Almost two-thirds of the U.S. industry-sponsored clinical trials begun for COVID-19 are testing agents designed to mitigate the disease’s clinical effects, while 28% are testing antivirals and 9% are testing vaccines.
Of the agents being studied to determine whether they mitigate the clinical impact of COVID-19, potential mediators of the immune system continue to represent the majority (62%) of those being studied. In addition, 10% of the studies are looking at products intended to improve or support lung function in severe infections, and another 10% are evaluating the effect of stem cells.
According to data from WCG CenterWatch iConnect, COVID-19 trial listings not only remain the most-visited listings as of September, but have jumped significantly since we last reported data. Starting in April, WCG CenterWatch iConnect has seen a continual increase in the percentage of traffic related to COVID-19, with COVID-19 trial listings representing 15.1% of total visits as of July, rising to 30.1% of traffic since. That aligns to continued public awareness and interest in trial progress, as well as progress of vaccine candidates moving into more advanced phases of development.
This week’s data show that even as states with the fastest-growing number of cases shift over time, states with the highest number of active COVID-19 trials has remained the same since the initial peak of the pandemic earlier this year.
Data from the WCG Knowledge Base™ confirm recently reported downward trends in new principal investigator trial participation. From 2015 to 2019, we saw a 48% decrease in principal investigators participating for the first time in industry-sponsored trials. This trend will be important to watch as we face a mounting backlog of trials in 2020 and beyond.
WCG is tracking trial starts by therapeutic area for quarters one through three of 2020 versus 2019. Even with overall trial start volumes down versus 2019, we do see an unsurprising uptick in the growth of infectious disease trial starts in 2020 versus other categories.
Nucleic Acids dominate the agents being studied in COVID-19 vaccine trials (40%), followed by Immune Mediators (30%). The mRNA-based vaccine platform being used in some vaccines is a novel one, not used in any currently approved vaccines.
WCG continues to track the progress of global interventional industry-sponsored COVID-19 trials that have been initiated so far this year – now numbering 412. Of those, 24 have been reported as complete, with five completing in the past three weeks since we last reported this data. To date, four studies have reported meeting their primary endpoint, with another four reporting they did not meet their endpoint. Notably, 127 studies are still planned for initiation in 2020, so this data will continue to reflect additional activity.
According to industry-reported data tracking planned study starts and actual study starts so far this year (including COVID-19 and non-COVID-19 trials), WCG is tracking more than 1,800 studies that were originally planned to initiate by August and are still showing a status of planned and yet-to-be initiated as of September. Though overall 2020 study start volumes are down versus 2019, more than 4,400 trials were initiated from January through August. We’ll continue to track this data in Q4 and beyond, as sponsors navigate uncertainty and update trial status and plans accordingly.
About a quarter of the industry-sponsored clinical trials for COVID-19 being conducted or planned in the U.S. as of Sept. 1 are studying agents in which the mechanism of action is primarily directed against the virus. Most of these agents are direct-acting antiviral therapies (50%), and antibody-based therapies (38%).
WCG identified a drop in the number of serious adverse reaction reports distributed between February and April by the pharmaceutical companies and CROs using WCG SafetyPortal. The timing of the drop corresponds with the pausing of studies and the slowdown in patient visits associated with the first phase of the COVID-19 lockdowns. Between April and August, however, serious adverse reaction report distribution has returned to pre-COVID levels, consistent with the restarting of research studies in many centers.
Of the industry-sponsored COVID-19 diagnostic device studies being conducted in the U.S. as of Sept. 1, 56% are looking at detection of the SARS-CoV-2 virus through genetic material or antigens, while 35% are looking for evidence of infection through antibodies generated by the person infected. A smaller number of products are being studied to detect specific COVID-19 signs and symptoms, such as ultrasound tools that can detect patterns of lung fluid abnormalities for rapid clinical diagnoses.
The number of Changes in Research (CIR) submissions related to COVID-19 peaked in April, at 58% of total CIRs, data from WCG’s Knowledge Base™ show. CIRs were driven by shifts to telemedicine and the shipment of drugs directly to study participants, among other factors. COVID-19-related CIRs continued to decline through July, representing just 13% of July CIRs.
Of the 381 industry-sponsored, global interventional COVID-19 trials, 88% are led by emerging and small pharmaceutical companies. Some of the notable new key players include BioNTech SE (Germany); CanSino Biologics and Sinovac Biotech (China); Ridgeback Biotherapeutics and Moderna (U.S.); and AbCellera (Canada).
Additionally, we are seeing a trend in partnerships, indicating the willingness of life sciences companies to collaborate on COVID-19 efforts for efficiency and speed. Noteworthy partnerships include:
Of the 295 non-COVID-19 industry-sponsored U.S. studies that have or had an original planned start date in 2020, 43% initiated at least one delay to their timelines, with a mean delay of 4.75 months. In a positive sign of recovery, since March, 63% of non-COVID-19 industry-sponsored U.S. studies that once reported being suspended have since restarted or completed.
There are 455 ongoing industry-sponsored clinical trials for indications related to COVID-19. The chart shows the number of trials in each global region; if a trial has clinical sites in multiple regions, it is counted in each one. Due to the global nature of the pandemic, multi-regional studies are common and important in developing COVID-19 therapies.
There are 43 industry-sponsored clinical trials for COVID-19 currently being planned in the U.S. Of the total, 31 have announced at least one delay to the originally planned study start date, with a mean delay of 1.8 months. That may reflect the aggressive goals of initial study timelines, as sponsors and researchers hope to move studies forward quickly and then have to adjust as start-up goals encounter real-life challenges.
Of the top 100 COVID-19 clinical trial listings attracting the most views on WCG CenterWatch iConnect, 53% are treatment related and 22% are vaccine trials, with the other 25% consisting of observational and diagnostic studies.
Despite making up just 22% of the trial listings, COVID-19 vaccine trials accounted for 35% of the views, indicating strong public engagement and interest in vaccine trial activity.
WCG is tracking the progress of the 359 global interventional industry-sponsored COVID-19 trials that have been initiated so far this year. So far, of 19 that have been completed, four reported that they’ve met their primary endpoint, while two did not meet their endpoint. With a significant volume of trials still in motion, we’ll continue to track their progress and outcomes.
Though contracting turnaround times are still longer than standard timelines in the U.S. (turnaround time up 13%) and EMEA (turnaround time up 10%), WCG is tracking a slight decrease in delays in both the U.S. and EMEA during May and July, with turnaround times down 2% to 3% versus March and April.
However, WCG data indicate that contracting for COVID-19 trials is moving much more rapidly, with ~57% shorter average turnaround times for COVID-19 specific trials as compared to all other trials.
This week’s data show that states with the fastest-growing number of cases in the past three weeks are currently under-represented in ongoing trial activity. Meanwhile, COVID-19 case counts are trending downwards in four of the top five states with the highest number of active trials. As sponsors consider new trial starts, the pace of the virus moving across states will be an ongoing factor and will force sponsors to be agile in site selection.
Increasing participant buy-in to trials post-pandemic is an issue of major concern to most sites responding to a recent WCG CenterWatch survey. Respondents anticipated that their biggest challenge would be attracting new participants and getting current participants back into trials, placing the issue above compensating for lack of resources and adjusting for missing trial data. Current trial participants and future trial participants will require additional communication and reinforcements from the site that safety precautions are in place to protect them from COVID-19.
More than two-thirds of the clinical trials initiated for COVID-19 are testing agents designed to mitigate its clinical effects, while 25% are testing antivirals and 7% are testing vaccines.
Of the agents that may mitigate clinical impact, most are mediators of the immune system. This group includes general immune mediators and cytokine blocking agents, stem cells and nitric oxide-based therapies that describe their intended mechanism of action as improving immune function and combatting the cytokine cascade associated with the severe pulmonary effects of the virus.
Almost two-thirds (61%) of sites surveyed said they plan to continue using remote coordinators, after the COVID-19 pandemic. Pre-pandemic, only 15% used remote coordinators, rising to 40% as quarantine conditions kept staff from working onsite. Remote coordinators support on-site staff by handling data entry, patient follow up and recruiting efforts.
As active U.S. industry-sponsored interventional COVID-19 trials continue to progress, we see a marked difference in planned trial durations, which maps to the relevant goals and endpoints of vaccine studies compared to treatment studies. As of early July, 83% of vaccine studies are expected to take five months or longer to complete, while 62% of treatment studies are expected to complete within four months.
The majority of active industry-sponsored, interventional COVID-19 phase II and III trials initiated in 2020 are scheduled to conclude within two months. These short study timelines reflect the realities of drug development for acute illnesses: study drug administration is brief, endpoint assessment occurs quickly, sites are opened to enrollment quickly, and the rate of participant enrollment becomes the major driver of study durations.
As expected, the conduct of healthy volunteer clinical studies was significantly impacted by the COVID-19 pandemic. In this assessment of global, currently active clinical studies, we can see that the number of study starts in the second quarter of 2020 began to recover.
In this analysis of global clinical studies for COVID-19 and COVID-19-related conditions, we see the current status (as of July 14) of studies that started in each month of 2020. The remarkable number of new study starts, including 741 in April 2020, reflects the rapid response of the global scientific community to quickly design and initiate studies to investigate both preventive and therapeutic measures for COVID-19.
The number of Changes in Research related to COVID-19 peaked in April, at 58% of total CIRs, data from WCG’s Knowledge Base show. The CIRs were driven by factors including shifts to telemedicine and the shipment of drugs directly to study participants.
The number of industry-sponsored COVID-19 trials running in the U.S. increased 26% during the last two weeks of June, reflecting the speed at which the industry is pursuing diagnosis, treatment, and prevention of the disease. We’re keeping an eye on total volume, as well as trial types, as we continue to monitor industry efforts to mitigate the pandemic.
As expected, there was a drastic increase in the number of industry-sponsored, non-COVID-19 trials disrupted in the first half of 2020 vs. the first half of 2019. Although disrupted trials account for a small fraction of the approximately 15,000 active trials in 2020, the seven-fold increase in disruptions versus 2019 represents a significant volume of trials impacted by COVID-19. 57% of the trials disrupted at the peak of the pandemic in April have since recovered, meaning they are either currently active or completed.
A recent survey of clinical trial sites revealed that the adoption of telemedicine by U.S. sites more than doubled during COVID-19, with 73% of sites now indicating they plan to use telemedicine going forward.
In the survey, 72% of sites indicated that prior to the COVID-19 pandemic, they “rarely” or “never” use virtual visits for clinical trial participants. During COVID-19, however, 64% of sites reported using telemedicine “sometimes,” “often” or “always.”
From January to May 2020, monthly non-COVID-19 trial starts averaged only 71% of last year’s pace, with the biggest drop unsurprisingly occurring in April and May. During those two months, starts dropped to half of last year’s starts in the same time frame.
However, if June continues at the current pace, it will likely meet or exceed June 2019 starts. That represents not only the highest percentage gain since the COVID-19 crisis, but also the nearest to 2019 levels so far this year.
Approximately 35% of non-COVID-19 industry sponsored trials planned and started in the US after May 1 are in oncology. The hastened recovery in certain therapeutic areas comes as sites and sponsors seek to address patients in need of critical care.
This week, 75% of sites indicated readiness to restart screening within the next four weeks – an appreciable jump since we began tracking in April. Meanwhile, only 4% are still uncertain about their timing for restarting – the lowest percentage since our surveys began, and a drop of 18 percentage points since June 9.
WCG is tracking more than 1,400 sites in 29 countries to understand how quickly total trial enrollment is being affected during the pandemic. 37% of sites responding are now open to enrollment of new participants, up 7 percentage points from last week, and our largest percentage increase since tracking began in March.
Total trial activity is dominated by interventional trials in the U.S. (88%), but we’re keeping an eye on growing demand for observational trials, which could have an impact on already burdened sites in hard-hit locations.
Among interventional trials, we’re tracking COVID-19 trials by product type. Since March 30, immune mediators have consistently represented 35% of total trial activity. But in the past two months, diagnostic device trials have overtaken antivirals as the second most-studied product type (20%). Interestingly, stem cell studies represent 7% of interventional trials.
This week’s data show that states with the fastest-growing number of cases in the past three weeks are currently under-represented in ongoing trial activity. Meanwhile, COVID-19 case counts are trending downwards in three of the top five states with the highest number of active trials. As sponsors consider new trial starts, the pace of the virus across states will be an ongoing factor and will force sponsors to be agile in site selection.
WCG is tracking more than 1,400 sites in 29 countries to understand how quickly total trial enrollment is being affected during the pandemic. 30% of sites are now open to enrollment of new participants, up two percentage points from last week.
Although overall industry-sponsored study starts have been declining, the industry is showing substantial signs of being ready for restart.
WCG is tracking more than 1,400 sites in 29 countries to understand how quickly total non-COVID-19 trial enrollment is being affected during this pandemic. 28% of sites are now open to enrollment of new participants, up three percentage points from last week.
Of sites surveyed, this past week showed a jump in optimism among sites that have not yet restarted screening. This week, 45% of sites indicated readiness to restart screening within the next two weeks – the highest percentage since tracking began in April. Meanwhile, 22% are still uncertain about timing for restarting, which is the lowest percentage since our surveys began.
WCG is tracking more than 1,400 sites in 29 countries to understand how quickly total trial enrollment is recovering. 25% of sites are now reopen to enrollment of new participants. Of the investigators who are restarting enrollment, 46% are reporting only being open to restarting enrollment for ongoing trials at their site.
Healthy volunteer study starts have been impacted more than almost any other type of research in 2020, down 73% from Q1 2020 to Q1 2019. We expect this number to be significantly lower – with a potential decrease of close to 90% – when we ultimately compare Q2 2020 to Q2 2019.
Across the more than 1,400 sites surveyed, more than 60% of those still closed to enrollment expect to restart enrollment in June. And only 23% of sites are reporting that they still do not have a target date for reopening clinical trial enrollment at their site.
More than 1,450 COVID-19 trials have been started in 2020, as the global number of COVID-19 cases reported tops 5.5 million. Of the 139 countries being tracked, 60% have more new cases reported in the last 5 days than in the prior 6-10 days… and those are just for the countries reporting case counts.
WCG is tracking more than 1,400 sites in 29 countries to understand how quickly total trial enrollment is being affected during this pandemic. 23% of sites are now open to enrollment of new participants – another 2 percentage point increase in the past week.
WCG is tracking more than 1,400 sites in 29 countries to understand how quickly total trial enrollment is being affected during this pandemic. The four countries showing the largest amount of clinical trial restart activity in the past week are the U.S., Israel, Poland and Ukraine.
21% of sites are now open to enrollment of new participants, an increase of 10 percentage points in the last three weeks. We anticipate this trend to continue as countries reopen.
Investigator restart comes in two forms – being open to enrollment of ongoing studies, and being open to enrollment of both ongoing and new trials. Very early data show that of the global sites that are restarting enrollment activity, 37% are open only to restarting ongoing trials, while 57% are open to enrollment of ongoing and new trials. 6% of sites are only open to new trials at this time.
That means that more than a third of investigators are still not willing to take on new trials that have been waiting to start since the COVID-19 outbreak. We will have more information on this next week.
WCG is tracking more than 1,250 sites in 29 countries to understand how quickly total trial enrollment is being affected during this pandemic. The total number of sites reporting that they’re open to enrollment increased this past week – from 13% to 15%.
WCG is tracking more than 1,250 sites in 29 countries to understand how quickly total trial enrollment is being affected during this pandemic.
For the first time in eight weeks, the total number of sites open to enrollment increased, up to 13%.
Although overall industry-sponsored study starts have been declining, the industry is showing substantial signs of being ready for restart. WCG anticipates that will result in a number of studies opening at the same time, with the largest number of planned restarts in the oncology space.
Sites surveyed May 2 were more than twice as likely to consider reopening enrollment in the next two to four weeks than when surveyed on April 25. The critical question becomes how sites will best support new trial starts and ongoing study restarts.
The number of US-based COVID-19 trial starts has tripled since March 30. During that time, the percentage share for immune mediators trials has grown from 21% to 35%.
WCG is tracking more than 1,250 sites in 29 countries to understand how quickly total trial enrollment is being affected during the COVID-19 pandemic.
In the last week, the total number of sites open to enrollment did not decrease, remaining at 11%.
When asked, 35% of sites said they could not estimate when they will reopen, and only 13% of sites said they could see themselves opening to enrollment by mid-May.
The COVID-19 pandemic has slowed down the overall turnaround time for clinical trial contracting between sites and sponsors. In the last six weeks alone, overall contract turnaround time across all trials has increased 12% according to EMEA data, while US clinical trial contracting time has increased more than 15%.
That said, there is one clear exception – on average, contracts for COVID-19 trials are being executed in less than 7 days.
The number of active COVID-19 industry-sponsored trials has more than doubled in the last four weeks to more than 150 trials globally.
Of note, four weeks ago sponsors were focused on antiviral trials, but there has been a significant shift, with the majority of industry-sponsored interventional trials now focused on immune mediators.
WCG is tracking more than 1,250 sites in 29 countries to understand how quickly enrollment is being affected.
As of this week, only 11% of tracked sites are currently open to clinical trial enrollment. That represents a percentage point decrease from last week and half the open sites from three weeks ago.
Of the 1,250 sites that WCG is tracking, 62% have a hold on enrollment due to sponsor-enforced, study-wide orders.
WCG has detected a 23% decline in both unexpected and expected serious adverse reaction reports in March and April across the largest pharma and CROs using WCG SafetyPortal. That indicates a slowdown in patient visits since the start of the COVID-19 lockdown.
Clinical trial activity continues to decrease globally, with only four countries projected to exceed pre-COVID-19 patient assessment volume during April.
That is down from March, when eight countries showed the same or more patient assessments for ongoing trials than in February.
The current US trials are operating on a fast enrollment pace, with 30 percent expected to be fully enrolled within 3 months.
More than 6,500 participants are currently needed to fill open slots in the 56 active COVID-19 industry-sponsored trials in the US. In the last six weeks, the US added two new trials, up from 54.
While investigators in New York are turning away study opportunities because of oversaturation and a lack of staff to support a clinical trial, sponsors should consider opening trials instead in New Jersey, Massachusetts, Pennsylvania and Illinois. Although oversaturation is not yet an issue in those states, sponsors may still have to augment site staff.
We’re tracking over 1,000 sites in 29 countries to understand how quickly enrollment is being affected. According to WCG Data, this week, only 14% of sites are reporting being open to enrollment – an 8% decrease just since last week.
100 non-COVID-19 trials have been placed on official hold within the last month, as compared to 12 trials put on hold the month prior to start of the pandemic impact.
According to WCG Data:
88% of sites reported an impact on study status due to COVID-19
79% of sites noted that they’re limiting enrollment at this time
Since January 1, there have been more than 400 COVID-19-focused studies started globally.
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