In short
- As funding for antibiotic development becomes increasingly uncertain, pharmaceutical companies must prioritize efficient clinical trials that maximize the chances of new drugs reaching the market. Precise management of finances and time is essential
- A large biopharma sponsor engaged PSI to support its pivotal phase 3 trial of a novel antibiotic for cUTIs
- Drawing on antibiotic expertise, collaborative site management, and a commitment to data quality, PSI supported the sponsor in completing the trial efficiently and in line with planned timelines
- A large patient population randomized
- All milestones met according to plan
- Despite the trial meeting its primary endpoint, the FDA requested additional data, prompting a rapid shift in strategy
- In response, the sponsor quickly reoriented, developing a new trial and placing continued trust in the partnership with PSI
- Choosing the right sites, with access to resources that enabled sites to focus on trial delivery, and assigning familiar and experienced CRAs meant that the trial was enrolled within an accelerated timeframe
- Data management was crucial – implementing lessons from experience with the sponsor and with cUTI meant that large volumes were handled by experts in line with study timelines
- Overall, a large number of patients were randomized, and milestones achieved as planned
- Ultimately, an independent data monitoring board recommended the trial met its predefined success criteria. The drug is poised to become PSI’s 5th approved antibiotic for cUTI
Enrollment
The challenge
A biopharma sponsor asked PSI to help conduct a pivotal phase 3 antibiotic trial for cUTI. These trials demand meticulous planning, significant time, and funding. On-time delivery and data quality were crucial.
Funding antibiotic clinical trials
Pharmaceutical companies have always struggled to secure funding for antibiotic development. There are multiple reasons for this [1]:
- Insufficient incentives: Prescriptions are acute, generating limited revenue per patient. Larger pharma sponsors tend to favor areas with broader reach, such as oncology, cardiology, or immunology
- Risky investment: Navigating infectious settings in clinical trials is complex and requires challenging patient recruitment to generate statistical power
- Low perceived value to health systems: New antibiotics are reserved to combat resistance, limiting both sales and economic impact
Each year in the USA, over 2.9 million patients with cUTIs are treated [2] at a cost of more than $6 billion [3]. Many require hospitalization and intravenous therapies due to limited oral options.
While broad incentives aim to reinvigorate the pipeline [4], running pivotal phase 3 antibiotic trials remains challenging, despite the obvious unmet need. Sponsors embarking on an antibiotic program must manage finances and time carefully and select the right CRO.
The solutions
The specifics
Proven antibiotic record: PSI’s strategy for delivering these studies has been tried and tested, as evidenced by our delivery of 50% of antibiotics to market since 2010. This approach ensures that our sponsors’ studies align with sites and regional standards of care, minimizing amendments and other potential delays. We also have experience working with BARDA, i.e., clauses in site and vendor contracts. We know which vendors and sites we can work with
Building the right team: PSI invests time and resources in establishing close site relationships. We know the sites our sponsors need to work with – not just those in major population centers, but across geographic regions. Sites prioritize our studies, and we understand their preferred methods of working and individual quirks. Pragmatic, evidence-based site selection in cost-efficient regions helped boost enrollment. PSI’s outreach plan informed sponsor decisions – including discussing sensitive contract negotiation strategies in advance
Committing to quality: Delivering high-quality microbiology data on time, as always, was crucial for the study’s success. PSI’s network of regional microbiology labs ensured the quality of data globally. Dedicated lab experts could investigate difficult isolates or sample tissues on the spot
Data expertise: PSI’s data monitoring team played a significant role – strategies such as monthly batch patient cleaning plans helped ensure sites were on top of data entry, while CRAs could maintain steady SDV on top of their workload. Granular-level isolate tracking was required for this trial, and was supported by an experienced data management team, lab team, and project managers
The outcome
The team enrolled a large patient cohort, and achieved key study milestones on time (first site activated, FPI, LPI, and DBL), which was important in this milestone-driven contract to share risks. PSI’s site selection strategy resulted in over 95% of sites enrolling patients, with a screen failure rate of 5% and an enrollment rate 23% higher than the industry average for this indication.
I am so impressed with the quality and follow through you show. I have worked with a lot of CROs and your team has outperformed anyone else I have ever worked with. You guys do a really good job and the dashboards and metrics are incredibly helpful.
But the story doesn’t end there
While the trial data suggested the sponsor’s intervention was noninferior to the SoC control, regulatory analysis led to a different decision and additional data were required. The sponsor had to change angles – so they turned again to PSI.
The team developed a data-driven, pragmatic plan aimed at implementing lessons learned and efficiencies from the prior trial to ensure success. The sponsor emphasized the importance of running this trial on, or even ahead of, schedule.
The second trial
PSI enrolled a large patient population across numerous sites and countries within an accelerated timeline. How did the accumulated experience factor into this exceptional enrollment rate?
Site choice
The choice of where to enroll doesn’t necessarily mean going to the large cities or capitals and picking the central hospitals. A network of sites can be more fruitful. The sites chosen for this study were long-term partners selected not only for their potential to enroll participants, but for their potential to significantly improve the study.
The chosen sites had access to a network of regional micro-laboratories, reducing the burden of some level of analysis. Regional micro-laboratories and laboratory specialists are not always available within the CRO landscape. Understanding the chain of custody – from patient to laboratory to database – was fully described in study plans and procedures.
Additionally, CRAs were familiar with the sites, which helped establish friendly and fruitful relationships. PSI’s CRAs were available 24/7: to guide and to take the lead in following study documentation and guidelines, allowing PIs to focus on treating patients.
Data challenges
In most cUTI trials, one of the main challenges is data volume. Sample sizes are high, and the number of data points needed from patients can amplify any challenges with the data. PSI’s history with the sponsor and with cUTI meant we were well-prepared and organized for the volume of data expected. One site had particularly high enrollment, which necessitated a pivot to a multiple-monitor visit strategy.
As in the previous study, sites focused on recruiting and treating patients, while CRAs and data managers ensured that the data obtained was valid and appropriate. Data management plans for data cleaning ensured that database lock milestones were met without issue.
The end result
An independent data monitoring committee recommended that the trial be considered complete following achievement of its primary endpoint.
Key takeaways
The course of a clinical trial is rarely smooth. PSI’s experience and solutions help sponsors overcome complex, time-sensitive challenges to bring new drugs through to approval. Driving results together is at the heart of what we do.
Accelerate your antibiotic clinical trial today
Abbreviations
BARDA, Biomedical Advanced Research and Development Authority;
CRA, Clinical Research Associate;
CRO, Contract Research Organization;
cUTI, complex urinary tract infection;
DBL, database lock;
FDA, Food and Drug Administration;
FPI, first patient in;
LPI, last patient in;
SDV, source data verification;
SoC, standard of care;
USA, United States of America.
References
1. Moll, N. European Antibiotic Awareness Day: Urgent Need for Sustainable Antimicrobial R&D to Combat Superbugs. 2024; Available from: https://www.efpia.eu/news-events/the-efpia-view/blog-articles/european-antibiotic-awareness-day-urgent-need-for-sustainable-antimicrobial-rd-to-combat-superbugs/.
2. Carreno, J.J., et al., Longitudinal, Nationwide, Cohort Study to Assess Incidence, Outcomes, and Costs Associated With Complicated Urinary Tract Infection. Open Forum Infectious Diseases, 2019. 6(11).
3. Lodise, T.P., et al., Hospital admission patterns of adult patients with complicated urinary tract infections who present to the hospital by disease acuity and comorbid conditions: How many admissions are potentially avoidable? Am J Infect Control, 2021. 49(12): p. 1528–1534.
4. Anderson, M., et al., Challenges and opportunities for incentivising antibiotic research and development in Europe. Lancet Reg Health Eur, 2023. 33: p. 100705.
