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F1RST Up®: Accelerating Clinical Trial Start-Up

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Source: Tufts CSDD, 2014, csdd.tufts.edu

In a 2016 survey of clinical research professionals, CSDD assessed clinical trial start-up practices and performance. The top-scoring study start-up process enhancements were:13

  • Central institutional review board (IRB) approval process (94.5 percent)
  • Standardized contracting for industry-sponsored clinical trials (90.1 percent)
  • Track site’s mandatory terms and previously negotiated language in greater detail to quickly get to study specific negotiations and/or determine if contracting will be a deal breaker (86.3 percent)

Frenova’s answer to addressing process enhancements and tackling other clinical trial inefficiencies typically experienced during a new clinical trial is F1RST Up (Frenova Rapid STart Up).

Launched in early 2016 and expanded in 2017, F1RST Up is an exclusive alliance of 23 clinical trial sites dedicated to renal research. The alliance includes 63 physician investigators and thought-leaders from across the country. F1RST Up investigators and their practice partners provide care to approximately 170,000 chronic kidney disease patients and 15,000 end-stage renal disease patients, collectively. A dedicated team of Frenova’s clinical research professionals manage and help orchestrate F1RST Up activities in close collaboration with alliance partners.

F1RST Up sites were invited to join the alliance following several months of meticulous planning and review of historical trial performance data. Candidate sites were assessed on:

  • Experience
  • Investigator engagement
  • Number of principal investigators and sub-investigators
  • Size of practice and patient populations
  • Systems and processes
  • Business strategy and acumen
  • Number, turnover, and experience of support staff
  • Strength of relationship with clinic staff
  • Achievement of patient enrollment targets
  • Strength and rigor of quality management systems
  • Quality as determined by previous audit findings

The F1RST Up alliance is configured and managed to accelerate clinical trial start-up in several ways. First, redundant contracting and protracted rounds of negotiating clinical trial agreement terms and budgets are minimized or eliminated whenever possible. In 2017, F1RST Up sites averaged 25 days to approve budgets and clinical trial agreement terms compared to 41 days for non-alliance partner sites and 57 days for the comparable industry benchmark.

Second, all F1RST Up sites use central IRBs, also known as research ethics committees, that simultaneously approve multiple sites’ participation in the same protocol. Using central IRBs has a profound, positive effect on contracting timelines, site activation, and the time until enrollment of the first patient. According to CSDD, sites using a local IRB (typically academic and research centers) took an average of 390 days from site selection to reach first patient enrolled, while sites using a central IRB reached this milestone on average in about 210 days.14 In 2017, F1RST Up sites were activated in 63 days from selection on average and took another 52 days on average to reach first patient enrolled, for a total of 115 days—nearly half the time of the comparable industry benchmark of 210 days.

Third, F1RST Up is leveraged to limit the number of sites required to meet trial enrollment goals, enhance protocol design and execution, and mitigate the likelihood of later enduring amends to the protocol. After being approved, poorly designed protocols are often amended once it is realized that timelines are slipping and patient enrollment is not as projected. CSDD reported that nearly all protocols require at least one amendment, with an average of 2.3 across all development phases.15 It is also reported that each amendment includes an average of nearly seven changes to its design. Approximately 37 percent of all amendments studied by CSDD were considered avoidable. According to CSDD, “On average the direct cost to implement a single protocol amendment is approximately $500,000 in unplanned expense and adds 61 days to the project timeline. This figure undercounts the full economic impact as it does not include the cost of internal staff time dedicated to implementing each amendment, costs or fees associated with protocol language translation, and costs associated with resubmission to the local authority.”16 CSDD also estimated that the total cost for trial sponsors to implement avoidable protocol amendments in 2014 was approximately $2 billion.

F1RST Up investigators are routinely engaged to help inform protocol design. As noted by CSDD, “The primary objective in optimizing protocol design is to perform great science that can be feasibly and cost-effectively executed.”17 F1RST Up investigators work with trial sponsors to tailor clinical trial protocols to the renal patient population by starting with the patient in mind. Equally important, F1RST Up investigators work to tailor protocols to the complexities of conducting research in the dialysis delivery business and operational environments. Protocol designs that are patient-centric, site-centric, and clinic-centric are best positioned to avoid costly and time-consuming future changes and amendments.

Fourth, because of their long history of conducting clinical trials, the sizable patient populations in their care, and the dramatically reduced contract and negotiation burden, F1RST Up investigators typically enroll twice as many patients into studies as non-alliance investigators. In one example, F1RST Up sites enrolled 22 patients during a six-month period compared to just five patients enrolled by an equal number of non-alliance sites during the exact same period and clinical trial (Figure 2).

F1RST Up investigators are often the highest enrolling sites among all sites globally participating in a clinical trial, including other research networks. Status as “top enroller” provides F1RST Up physicians the opportunity to develop deep subject matter expertise in a certain therapy or therapeutic area, which often leads to serving as a key opinion leader, a national clinical trial leader, and/or an expert advisor to trial sponsors. To understand best practices in clinical development, CenterWatch recently interviewed trial sponsors considered to be best in class for speed to approval. Among the factors noted for contributing to development speed was building strong relationships with investigators.18 Strong investigator-sponsor relationships typically extend beyond product approval and into product launch preparation and commercialization.

F1RST Up and the breadth of Frenova’s clinical research activities that span and accelerate the path to approving new drugs and medical devices also facilitate the commercial introduction of these new therapies into the standard of care for patients. Leveraging Frenova’s relationship-building activities across an ecosystem of renal care stakeholders—including clinical research investigators, trial sponsors, patients, patient caretakers, clinicians, and leaders in business and medicine—accelerates the speed to product launch and commercialization. This achieves Frenova’s mission to advance the science of renal therapies and help bring novel treatments to market for patients with renal impairment.

FIGURE 2 | Patient enrollment rates, F1RST Up vs. non-alliance sites

Meet Our Experts

Kurt Mussina
Vice President, Clinical Studies Operations, Frenova Renal Research

Chemist, executive, and entrepreneur, Kurt Mussina leads FMCNA’s contract research organization, a world-class network of more than 450 principal investigators across 260 research sites. A former analytical chemist and research and development scientist for Teva and Novartis pharmaceuticals, he holds a bachelor’s degree in chemistry from Montclair State University and a master of business administration from the Fuqua School of Business at Duke University.

Christina Kahn
Senior Director, Site Alliance Management, Frenova Renal Research

Christina Kahn oversees all trial activities occurring at research sites staffed by Frenova throughout the life of the trial, including oversight of research site protocol adherence, data quality, patient safety, site payment, regulatory obligations to the FDA and IRB, drug accountability, and site performance. An author of numerous publications, she is a certified clinical research professional and an affiliate member of the American Society of Nephrology. She earned her bachelor’s degree in biology with highest honors from Purdue University.

References

F1RST Up®: Accelerating Clinical Trial Start-Up
by Kurt Mussina, MBA & Christina Kahn

  1. Mullin, R. Tufts study finds big rise in cost of drug development. Chemical & Engineering News, November 20, 2014. https://cen.acs.org/articles/92/web/2014/11/Tufts-Study-Finds-Big-Rise.html.
  2. Bolten, BM. Fastest drug developers and their practices. The CenterWatch Monthly 2017 Aug 1;24(8). https://www.centerwatch.com/news-online/2017/08/01/fastest-drug-developers-practices/.
  3. Ibid.
  4. Getz K. Improving protocol design feasibility to drive drug development economics and performance. Int J Environ Res Public Health 2014 May;11(5):5069-80. doi:10.3390/ijerph110505069.
  5. Lamberti MJ, Chakravarthy R, Getz, KA. Assessing practices & inefficiencies with site selection, study start-up, and site activation. Applied Clinical Trials, August 5, 2016. http://www.appliedclinicaltrialsonline.com/limited-boosts-study-start.
  6. Lamberti MF, Wilkinson, M, Harper B., Morgan C, Getz K. Assessing study start-up practices, performance, and perceptions among sponsors and contract research organizations. Therapeutic Innovation & Regulatory Science, January 11, 2018.     https://doi.org/10.1177/2168479017751403.
  7. Fenichel M. Site selection a continuing conundrum. The CenterWatch Monthly
    2017 Sep;24(9).
  8. Ibid.
  9. Lamberti et al. Assessing study start-up practices. https://doi.org/10.1177/2168479017751403.
  10. Bolten. Fastest drug developers. https://www.centerwatch.com/news-online/2017/08/01/fastest-drug-developers-practices/.
  11. Fenichel M. Site selection a continuing conundrum.
  12. Getz, KA. Enrollment performance: weighing the “facts.” Applied Clinical Trials 2012 May 1;21(5). http://www.appliedclinicaltrialsonline.com/enrollment-performance-weighing-facts.
  13. Lamberti et al. Assessing study start-up practices. https://doi.org/10.1177/2168479017751403.
  14. Ibid.
  15. Getz K. Improving protocol design feasibility. doi:10.3390/ijerph110505069.
  16. Ibid.
  17. Ibid.
  18. Bolten. Fastest drug developers. https://www.centerwatch.com/news-online/2017/08/01/fastest-drug-developers-practices/.