This article is part 2 of a multi-article series about the Shark Tank Initiative, to read part one click here

 Collaboration is Key

The most productive approach to solve challenging and critical issues, according to Dr Francis Collins of the NIH, brings together groups of experts with varying skill sets. In this setting, individuals worry less about who will get credit, and more about just getting the job done. Having previously led similar partnerships to develop next generation therapies for conditions such as Diabetes, Alzheimer’s, Rheumatoid Arthritis, Lupus, Parkinson’s and cancer, and Dr Collins has found them enormously productive. His philosophy – get the best and brightest scientists around the same table to design the work, hold themselves accountable and ensure data accessibility to everyone. When the COVID-19 crisis came along, Dr Collins recognized this same model could meet the challenges presented by the novel coronavirus. Colleagues across all sectors agreed. This marked the beginning of the Shark Tank and RAD-X Collaboratives.

Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)

The senior leadership of the committee convened for the first time on April 3, and included  pharmaceutical companies, representatives from the FDA, CDC, BARDA, NIH and the European Medicines Agency, in order to discuss COVID-19 challenges best solved collectively, rather than by any one sector or agency alone. This became ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines). While it had taken years for Dr Collins to form prior partnerships, this took just two weeks.

On April 17, the NIH announced the launch of the ACTIV collaboration. It involves 18 pharmaceutical companies, multiple academic experts, the FDA, CDC, BARDA, European Medicines Agency, the Department of Veterans Affairs, and the Department of Defense. Dr Collins and Paul Stoffels, Vice Chairman of the Executive Committee and Chief Scientific Officer at Johnson & Johnson, co-chair the initiative. The executive committee consists of senior industry leaders and experts from NIH and FDA. The partnership works on COVID-19 related solutions 24/7.

How it Works

Comprised of four work groups, each co-chaired by senior scientists from both industry and the NIH, ACTIV ‘s scope includes a clinical therapeutics group currently conducting rigorous scientific review of approximately 170 identified therapeutic candidates to move those of greatest urgency into clinical trials. The organization will focus its financial resources on the most promising treatments. At the same time, another group focuses on maximizing clinical trial capacity to test the highest priority candidates. It standardizes evaluation methods in order to speed FDA review. This represents an “unprecedented” level of coordination, according to Dr Collins.

Members of the ACTIV initiative have embraced the partnership and committed to prioritizing treatments based on potential. Beyond that, they have indicated their willingness to contribute their clinical trial capacity, regardless of ownership of the selected pharmaceuticals. Dr Collins calls this “A partnership in the truest sense of the word.”

Need for Accurate Testing Never More Clear

With the continuously rising death toll in the U.S., Senator Maggie Hassan (D-NH) stated that the need for testing has never been more clear. Despite this, she notes, testing remains inaccessible to large segments of the population. Beyond that, some research indicates COVID-19 testing inaccuracies between 15 and 30 percent of the time. She wonders how the NIH will ensure production of high quality, accurate diagnostics. Dr Collins insists that Phases 1 and 2 of the Shark Tank initiative and RAD-X processes will weed out inaccurate diagnostic products. Products selected for production and distribution will undergo intense FDA scrutiny for Emergency Use Authorization. This will validate their accuracy. Senator Hassan further questioned how the committees would ensure new diagnostics represent a significant improvement over existing test kits. Dr Collins assured her of BARDA’s commitment to identifying truly innovative solutions.

Shark Tank

The NIH, in concert with BARDA, has created a program inspired by the reality TV show, Shark Tank. The initiative intends to inspire competitive innovation in the private sector for rapid diagnostic technology. Fed by BARDA and the NIH, the Shark Tank accept applications and proposals through a few different, but collaborative, programs.

While Senator Jacky Rosen (D-NV) agrees that the competitive nature of the Shark Tank would spur developers on. However, she raised concerns that it might result in unintended consequences. For example, wishing to protect and promote their own projects above others, might self-silo. Such a response, she posited, could result stifle collaboration. Dr Collins countered that the Shark Tank organically discourages siloing by the very nature of the organization. Specifically, developers work side by side with well-connected members of the business community who partner them with companies capable of scaling their technology to the necessary level. So, yes, there will be competition, and obviously successful companies will want to come out on top. “That’s the success of American capitalism, and it’s what we need in this space”, Dr Collins explained.

Despite Senator Patty Murray (D-WA’s  appreciation for the Shark Tank, she wants everyone to remember that the fight against COVID-19 “is reality, not reality television.”  Any response should be led by scientists and must “prioritize public health, not profits, not politics.” While innovation plays an important role in the development of vaccines, treatments and tests, “there is no silver bullet.”

Rapid Acceleration of Diagnostics (RAD-X)

The NIH responded to the need for increased testing capacity by launching RAD-X – Rapid Acceleration of Diagnostics during the last week of April. Most current testing relies on detection of the SARS-CoV-2 RNA genome using polymerase chain reaction (PCR). PCR takes small segment of RNA and amplifies it millions of times over to make it detectable. Not only is PCR time consuming, but it requires a laboratory with a thermal cycling machine and personnel familiar with running the test and troubleshooting problems. On the other hand, RAD-X, aims to engage scientists across the country to develop more advanced diagnostic technologies. It will increase testing capacity by millions of units per week by end of summer, with even greater availability by flu season. In this way, it will also increase access to testing.

A bottom-up partnership, most of the talent, innovation and creative ideas for RAD-X testing platforms comes largely from small businesses. In this initiative, the private sector feeds their ideas into the Shark Tank. The RAD-X/Shark Tank initiatives accept applications on a rolling basis. By May 6, the collaboratives had 1087 applications initiated, with 79 complete. Of the 1087 already received, two-thirds are from small businesses.

RAD-X – Multi-Phase Initiative

The RAD-X diagnostics initiative consists of multiple phases. The first phase, a call for innovative technologies, occurred on April 28. During Phase 0, clinical, business, technology and regulatory experts perform a one week rapid evaluation of proposals. The experts ensure proposals fit the model and identify the “gems”. Phase 1, grants inventors a modest financial award and provides support from the RAD-X committee to address scientific and business weaknesses ascertained during the review process.

Of the 1087 Shark Tank applications, the expert review team has identified 20 completed applications already prepared to move into Phase 1’s more intense scrutiny. Beyond that, Dr Collins further noted that some proposals are developed enough that they will move directly to Phase 2 without first passing through Phase 1. Even better, some proposals are already well-developed enough to move forward, and will progress directly to Phase 3. They will receive the necessary support to scale-up for testing, validation, regulatory requirements, supply manufacturing and distribution, working closely with colleagues at BARDA. In his 27 years at NIH, Dr Collins has never seen anything move so quickly.

Antibody Testing is Not Included in RAD-X or Shark Tank

Senator Rosen inquired as to whether antibody testing should be included in the Shark Tank. According to Dr Collins, antibody tests are one area they feel the commercial community has done a good job in terms of production and distribution. At the request of the FDA, the National Cancer Institute (NCI) has validated the sensitivity and specificity of these tests. Therefore, at the present time, experts do not see a need for government involvement in this field of diagnostics. On the other hand, Dr Collins noted, should a new technology offer the ability to test for both antigen and antibody response simultaneously, the NIH and BARDA would likely get involved.

Concern for Alaska’s Coming Fishery season

Senator Lisa Murkowski (R-AK) expressed her concern about Alaska’s fisheries as their season begins May 14. The five processors operating in Cordova bring in an average of 450 seasonal workers for a total 500 workers. On May 6, Cordova identified its first COVID-19 case, a seasonal worker who had come in from out of town. She has concerns about RAD-X-UP. Rural Alaska needs point of care testing, not because they are hard hit, but to prevent a hard hit that would likely result in fishery closures, “What are you gonna give me?” she asked Dr Collins.

Dr Collins responded that by the end of the summer, Shark Tank aims to provide them with point of care testing that offers results within one hour. This would allow them to not only test newly arriving employees, but to test all employees on a weekly basis to prevent a large outbreak with highly affordable and highly accurate tests. He further noted that participation in RAD-X-UP doesn’t necessarily exclude places that are not hard hit, if they are vulnerable and lack adequate access to testing.

Resolving Access Inequity in Underserved Populations – RAD-X-UP

Part 3 of the initiative focuses on the implementation of strategies to enable testing of rural, underserved and under-resourced populations. While these populations are among the hardest hit by coronavirus, they are often among those most lacking in access to testing. They call this initiative RAD-X-UP – Radical Acceleration of Diagnostics for Underserved Populations. In addition to advancing diagnostic technology, RAD-X-UP involves the creation of testing centers across country in hard hit areas where testing has been most inaccessible. It will focus on ethical, legal and social issues associated with access inequity.

During his questioning, Senator Pat Roberts (R-KS) expressed concern regarding the ability to keep meat packing plants in his state open, due to the fact that employees are becoming infected. He expressed a need for education for plant employees – who speak 50 or more languages – as well as point of care testing to ensure employees are not sick or asymptomatic carriers when clocking in each day. These are exactly the sort of problems, according to Dr Collins, that the RAD-X program aims to solve.

Senator Bill Cassidy (R-LA) discussed the hard hit Louisiana, a state with many underserved populations, has taken from COVID-19 and inquired about how RAD-X-UP would help them. He wanted to know how they apply for it, how they get it and what resources are allocated. Because the funding for RAD-X-UP has just recently come along, Dr. Collins explained they are still in the process of pulling the program together. That said, they will solicit applications for centers in locations where underrepresented and underserved groups are hard it and lack the access to testing experts would typically like to see, “Watch this space, it will be coming,” Dr Collins assured Cassidy.

Squeezing Capacity Out of Existing Technology

When Senator Lamar Alexander (R-TN) asked Dr Collins about squeezing “all tests out of existing tech”, Dr Collins replied that BARDA can assist with scaling up existing diagnostics, but that most current testing takes place in laboratories, they’re not point of care. Ramping up point of care shows particular promise due to its accessibility to underserved areas and populations, as well as its more rapid turn around time. So, yes, Dr Collins replied, we need higher throughput of existing diagnostics, but we also need innovation in this area.

Senator Mitt Romney (R-UT) questioned Dr Collins about the Abbott ID-Now diagnostic machine, and why the U.S. can’t just produce many more of them to make it available at most businesses. Dr Collins explained that while it is a great machine, and provides point of care results quickly – within 15 minutes – there are only about eighteen thousand of the machines currently in use in the U.S. In order to roll out the ID-Now machine on a large scale, production would need to increase exponentially, and this is a rather expensive machine.

On top of that, Dr. Collins noted, the machine has about a 15 percent false negative rate, so they are looking for something with a higher degree of accuracy. Senator Romney continued his questioning regarding the Abbott ID-Now machine, inquiring as to whether the government could devote significant resources to these machines, perhaps have experts focus on making it more sensitive and accelerating production in larger numbers in order to realize its full potential, rather than hoping for a better design from the Shark Tank. While this is one of the most exciting options right now, Dr Collins believes they can do better through the Shark Tank initiative.