The Last Stretch for Moderna’s COVE Study: Targeted Trial Site Numbers in South Texas Don’t Jibe

The Last Stretch for Moderna's COVE Study Targeted Trial Site Numbers in South Texas Don't Jibe

Centex Studies Inc (Centex), in partnership with Valley Medical Arts Clinic, was selected by Moderna as one of at last 87 trial site organizations to recruit and administer the mRNA-1273 experimental vaccine as part of the pivotal and closely watched Phase 3 clinical trial known as the “COVE study.” Located in the heavily Hispanic Rio Grande Valley area in southern Texas, Centex commenced enrollment activities starting mid-July while the study formally launched on July 27, 2020. With a reported 87 trial sites and a target of 30,000 volunteers, on average each site would need to recruit, enroll and treat 344 volunteers. Although by September 11, Moderna reported a total of 23,497 volunteers enrolled in the COVE Study, the sponsor lags behind in its minority (primarily African American and Latino) recruitment targets, making Centex and other select Texas sites key for Latino participation. Although the trial site management organization already has enrolled 400 participants it’s still short of its lofty target by at least 1,000 volunteers, as this highly respected, independent trial site management operation signed up for a total of 1,800 participants or 6% of the total patient base for this study, according to local news. TrialSite commends Centex Studies first and foremost because it carries disproportionate responsibility for volunteer recruitment and enrollment. Although with less than 7,000 volunteers to go to complete this study, it appears this last stretch of recruitment and enrollment introduces some challenges. The following is a breakdown of the current situation.

Pressurized Trials

The current batch of COVID-19 Phase 3 study vaccine study sponsors face far more than the typical pressure associated with aggressive, often unrealistic study timelines. This is for three reasons. First and foremost, is the pandemic itself. The worst public health crisis in a century, nearly 200,000 have died in just over half a year in the United States alone. Calls for a vaccine are urgent and this, of course, translates to enormous weight on trial sites. Secondly, billions of taxpayer money are injected into these biotech/pharma companies, making them completely subsidized by the government and further subject to various societal pressures. For example, Moderna has received in aggregate nearly $1 billion for research support and another $1.5 billion in vaccine orders. These kinds of figures are naturally associated with high stake, high pressure affairs. Of course, Moderna’s executive team have benefited nicely with windfall payouts thanks to the automated stock trading scheme, which adds even more pressure on the company as a whole. But yet another even denser, more volatile layer of pressure escalates: the politicization of science during this pandemic in the context of the presidential election season.   

For this third point, although the President has certainly led the charge calling for a vaccine ready before the end of the year, the entire political class has bought in, signing up to allocate—essentially handing out billions of dollars with less than transparent oversight. Hence, due to A) the pandemic, and B) the enormous sums of public money pumped into biopharma, and C) the politicization of science due to an election season lead to what most certainly are variables contributing to unreasonably high expectations. 

Yet amazingly Moderna, NIAID/BARDA and the trial sites are so close to the finish line with 23,497 volunteers already enrolled by September 11, 2020. With 50 days remaining to the election day, if the sponsor and its trial sites kept up this torrid pace of volunteer enrollment, they would be able to wrap up on, or before, the end of the month. But problems appear ahead.

Remarkable Burst of Volunteer Enrollment

Now with all of this in mind comes the current batch of COVID-19 vaccine trials and the topic here: the COVE Study.  Again, this study was designed under enormous pressure amid millions of COVID-19 cases worldwide, record deaths in combination with large sums of public money and an aggressive, business-minded White House that established a competitive, almost zero sum game environment—get a safe and effective vaccine done by election day, period. 

Although on August 10, CNN actually got a hold of an internal Moderna email to principal investigators, reporting that the sponsor, along with co-sponsor collaborators National Institute of Allergy and Infectious Diseases (NIAID) and Biomedical Advanced Research and Development Authority (BARDA), had recruited at that point a total of 4,536 study enrollments. This equated to an average of 311 new enrollments per day as the study commenced on July 27th. CNN reported at the time, that at that rate, the study wouldn’t enroll the target number for over three months, meaning the completion of the study would miss the November election date.

But the sponsor, its government partners and, importantly, the trial site organizations, moved into full throttle and by the end of Friday, September, 11 had enrolled a total of 23,497 volunteers in the 46 days since study start of the study. This equated to an average of 511 new volunteers per day.   

Clearly since that August 10 email, the sites have stepped up in a tremendous effort. Using election day as a milestone, the study only has 6,503 volunteers remaining and 50 days. If existing sites kept up their averages, this study would conclude within two weeks!

But there’s more to the story as it would appear the sponsor faces A) rapidly declining participation rates, and B) intensifying pressure to recruit minorities, a challenging objective with so little time.

Enrollment Markedly Slows Down

Moderna and all of its approximately 87 trial sites recruited a total of 2,806 new volunteers from Friday, September 4 to Friday, September 11. Equating to an average of 298 participants per week, the average weekly recruitment total plummeted from even the early troubled start reflected in the internal email back on August 10. If this figure is the new norm for recruitment per week then they would still be able to wrap up the study prior to November but the additional complexity is the requirement for more minority participation.

Unrealistic Expectations for Minority Participation?

TrialSite reported on September 6th that pressures grew on Moderna to recruit more minorities. NIH Director Francis Collins assigned Moderna a “C” grade for its results thus far in regards to minority participation. Frankly, given historical challenges with minority participation and the incredible progress Moderna made in averaging 511 volunteers per day nationwide, the “grading” by NIH seemed hardly fair.

But with increasing pressure to recruit at-risk groups, namely ethnic minorities, Moderna commented by early September that it may have to slow down the recruitment pace to pick up more minority enrollments. The mandate was clear by September 4, yet a week later on September 11 the minority participation rate went up just one percentage point (26% to 27%) with the addition of 2,806 new study participants. Now with 27% of the total “diverse communities,” the company does report growing percentages of Blacks and Latinos week over week but the emphasis on precise minority targets rates renders this study increasingly difficult to complete in a reasonable time frame. Put another way, do federal research bureaucrats put a timely conclusion at risk now and go forward or is the targeted minority participation benchmark absolutely necessary based on risk profiles of the pandemic and patients?

This intense focus on minority participation places burdens on particular sites in heavily Hispanic parts of Texas, such as McAllen, where Centex Studies operates. According to some accounts, of the nearly 100 sites within the countries involved with the Moderna study, U.S. Rep Henry Cuellar reports Texas trial sites are forced into an additional over time with participant recruitment, commenting, “They purposely cover a lot of the areas that have high numbers of minority communities” at a news conference back on July 27. Representative Cuellar continued, “And that’s why the McAllen area, the Valley area, the Laredo area, the San Antonio area are extremely important.”

Enter Centex Studies Inc.

Centex Studies Inc., a Texas-based trial site management organization profiled by TrialSite previously, recently utilized local media, including The Monitor, to drive attention locally to the importance of this pivotal clinical trial. Due to the pressures already discussed, this successful but relatively small research site management operation would need to carry a heavy weight moving forward.

The firm, apparently still independent and founded by Devora Torrence back in 2006, has developed extensive ties to the community, which has led to results in past trials. That attracts more sponsor business and hence why the firm has been able to expand to four locations (three in Texas and one across the border in Lake Charles, Louisiana).  

Ms. Torrence shared her gratitude for all the community has done, sharing in the recent press, “The people of McAllen have gone above and beyond our expectations” she declared. Further emphasizing the support in this Rio Grande Valley community, “They are so willing to play any part they can in beating this thing, and we couldn’t be more grateful for their contributions to research.”

To execute the study in the Rio Grande Valley region, Centex Studies paired with Valley Medical Arts Clinic and a total of about five physicians as well as Lee’s Pharmacy.

Numbers Don’t Jibe

This community connection, as it turns out, becomes important in the high stakes COVID-19 vaccine race as the firm’s McAllen site operation, the nexus for this activity, operates in a region where 91% of the 1.4 million people are of Hispanic origin.

With an urgency for the study to pick up more minorities, it’s no wonder that Centex Studios felt compelled to act and shoot for what appear to be overly ambitious numbers. And the numbers appear off. For example, according to their (Centex) own account, they have recruited 400 participants in the 46 days since the study commenced. This averages out to about 9 volunteers per day and more than likely based on the population to be about 90% Hispanic/Latino participants. Put another way, Centex, which is a small independently-owned operation, has recruited about 1.7% of the total volunteers for the study thus far. In the recent press, conflicting numbers were shared as it was announced that they needed 1,000 more volunteers (this would equal 1,400) yet also in the same press account their target was pegged at 1,800 volunteers.

Yet in a previous report, the targeted number for the site’s contribution was 500 volunteers, which given the size of the trial site management firm’s operation seemed rationale representing 1.6% of the total number of participants.

Now with just 6,503 volunteers remaining to hit 30,000 for the study, this small independent operation appears pressured to pick up 15% of the total remaining volunteers! This doesn’t make sense as they have again averaged 9 per day since the study start date. At current averages, the entire study would be delayed by months.

Monitoring COVID-19 Vaccine Studies

TrialSite will monitor these pivotal studies carefully. Given the online media platform’s mandate of greater research transparency and accessibility, a few more eyeballs on these Operation Warp Speed-financed studies will benefit all.  That specific trial sites are compelled to recruit so many participants in so little time represents a concern for ongoing observation.

Lead Research/Investigator

Joel Solis, MD 

Call to Action:  Those that live in the Rio Grade Valley and are interested in learning more can see or call 281-918-0048.