January 11, 2021 | by Luke Morales
The National Center for Advancing Translational Sciences (NCATS) realized a problem: on average, new medications were taking more than 10 years to go from basic discovery to the marketplace with only a 12 percent success rate for medicines that go to clinical trials. Of those medications, a study published by the American Medical Association found the average cost per FDA-approved drug was $985 million.
Translation (turning scientific observations into medical interventions) requires clinical trials. NCATS realized that even though their Clinical and Translational Science Award recipient institutions (CTSAs) existed within the same network, clinical trial protocols for each were different, making the most impactful multi-site studies difficult to conduct. Regulatory approval processes and implementation strategies fluctuated from location to location, and each institution innovated within a vacuum. The solution? TIN.
What Is TIN?
TIN is the Trial Innovation Network, which streamlines clinical trials and harnesses the collective power of NCATS-funded institutions. As NCATS explains, TIN creates a “national network that focuses on operational innovation, excellence and collaboration and will leverage the expertise and resources of the CTSA Program.” Of the 62 CTSAs nationwide, Wake Forest, Duke and UNC form the triad of CTSA hubs in North Carolina. Wake Forest’s TIN program leaders are Selvin Ohene, Director of the Office of Clinical Research, and Cheryl Bushnell, MD, professor of Neurology.
Ohene says that industry-funded clinical trials have taken a hit during the coronavirus pandemic, but grant-funded clinical trials and COVID-19-focused clinical trials have buoyed the School of Medicine in this season. As NCATS Director Christopher Austin, M.D., has reported, “The rapid expansion of these [COVID-19] clinical trials demonstrates how nimbly the network of CTSA Program hubs and the TIN can respond to the nation’s research needs and shorten the path from discovery to treatment.”
Multi-Site Study Opportunities
Wake currently has many active COVID-19 studies, some which came directly through the network. “TIN has been charged with collating opportunities related to COVID-19 on behalf of all the CTSA hubs,” Ohene says. “…they've been able to organize these opportunities for us in a way that we can digest them as a site to figure out which opportunities are best for our patients… I don't think that we would have had access to ACTIV-1 had we not been a TIN member site.”
| ACTIV-1 CLINICAL TRIAL: Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) |
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| ACTIV-1 is a Washington University-led study investigating Immune Modulators for treating COVID-19. Wake Forest site involvement is led by Dr. Caryn Morse, Internal Medicine, Infectious Disease. This advanced study enrolls adults already hospitalized with COVID-19. As described by the NIH, “The ACTIV-1 master protocol will test promising immune modulator compounds, a class of drugs that help minimize the deleterious effects of an overactive immune response to SARS-CoV-2 infection. |
Since 2017, the network has made 30 studies available to Wake Forest. For 19 of those studies, Wake Forest designated a local Primary Investigator (PI) to lead their site participation. (The remaining 11 studies were not matched because Wake Forest did not have the correct patient population, was already running competing trials, trial budget was prohibitive, or there was no PI available in the required focus area.) Why does access to more studies benefit the institution? Ohene says, “It's hard to get access to these important national investigator-initiated study opportunities if you're not connected or part of other research networks. You won't know about these opportunities. And then we won't have those opportunities available for patients here at Wake Forest.”
“Operationally,” Ohene concludes, “TIN provides us with the organization to actually put this all together. Like, we've already kind of been doing this, but the TIN really helps us connect the pieces so that the resources that we provide are a lot more fluid.”
Taking Your Research to the Next Level
Bushnell reports Wake Forest’s participation in national trials gives increased visibility and opportunity. “It really benefits both faculty and the institution.” But from another angle, Bushnell focuses on the network being the perfect resource for early- or mid-career researchers ready to advance their research—whether to increase NIH-scoring of study readiness or engage in multi-site clinical trials at a national scale. TIN increases the success of these endeavors by refining study design before funding submissions and through opening up the network of potential collaborating CTSA sites.
Bushnell asks researchers, “Are you interested in taking your study to the next level? You've got preliminary data from your pilot study, maybe it's time to think about NIH or other funding, that the TIN can provide you [consultation services] early on in the design process. They can help. They can also help once you already have a study funded and you need help with recruitment. So I think the multi-faceted services is truly a benefit.”
Build in the Time: TIN Consultation
Nationally, 309 study proposals have been submitted to the network for initial consultation to date. In a 2018 publication, the Journal of Clinical and Translational Science reported an average 85 percent satisfaction rating from respondents. Of these, 80 percent indicated “they ‘Strongly Agree’ with the feedback and recommendations they received from the consult.” While these numbers may only be anecdotal, they do point towards an exciting corroboration of TIN’s value.
What might keep a researcher from taking advantage of this free consultation service? Time. Ohene recommends submitting 3-6 months in advance of funding deadlines, which can feel steep in the nascent stages of study design. “But I would encourage faculty that are writing proposals, writing grants, and they're not getting the score that they desire to get funded might want to consider submitting their proposal to the TIN and seeing if the TIN can help them get their proposal to a place where it can get funded.”
“For me, personally,” says Bushnell, “I think that the more external review of your grants you have before you submit, the better.” After some initial rockiness in its 2016 launch, TIN has optimized the proposal submission process, offering applicants a clear submission timeline (above) and FAQ for what makes a good proposal. Bushell applauds these improvements: “They definitely have a much better organized system now than they did a few years ago.” Bushnell repeats, “if you do put in that extra time before you submit, you could end up with a much better proposal and have a much better chance of funding. So build in the time.”
| TIN’s Recruitment Insights: Underrepresented Minority Groups |
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The US POINTER goal was to recruit 30 percent of participants from communities particularly at-risk for dementia and Alzheimer’s disease and traditionally underrepresented in research. Hill says, “The [RIC] helped fortify some of the directions we needed to go in in terms of our inclusive grassroots recruitment strategy.” The RIC helped Hill’s team examine their recruitment marketing strategy to address the negative perceptions of clinical trials within their target populations. “We were hitting the negative statistics pretty hard,” Hill says. With the RIC’s insight, Hill’s team was able to pivot to ask the question “Can this be something that we can get [participants] excited about and actually instill a sense of hope in our communities?" These efforts have been helping the study reach its recruitment goals throughout its national recruitment regions. |
The TIN’s How to Participate
The Trial Innovation Network exists to optimize and accelerate multi-site clinical trials. Given the international urgency around the Coronavirus pandemic, NCATS says the network “will play a key role in working to add study sites and enroll patients, including those from communities disproportionately affected by COVID-19.” There has never been a time more apt for utilizing the network. More information can be found by visiting trialinnovationnetwork.org. Review their proposal process and submission overview to see how your study might be a good fit for TIN. Additionally, Wake Forest investigators can reach out to Selvin Ohene directly at sohene@wakehealth.edu for recommended next steps facilitating TIN proposal submissions.