Lessons Learned From a Phase II Influenza Clinical Trial
January 13, 2020
In this post, we discuss elements and lessons learned from a recent BARDA funded Influenza A Phase II study. The study’s purpose was to assess the efficacy of the Sponsors IP in treating severely ill and hospitalized Influenza A patients.
- The study was targeted to enroll a subset of the general Influenza A global population. The study inclusion criteria required that each patient be ill for a certain number of days which could not be exceeded. The subject must also be hospitalized and specifically on oxygen therapy.
- This global study enrolled patients between late 2017 and early 2018 to maximize participation during the active flu season.
Peak Flu Season*:
- Northern hemisphere = October through May
- Southern hemisphere = May through October
*Based on data supported by WHO and CDC
MAPPING THE LANDSCAPE AND ASSISTING PATIENT ENROLLMENT
Since we were dealing with a subset of the overall patient population with Influenza A, we had to cast a wide net. The desired study population required specific timing and a specific location/state. We had to catch patients within a certain number of days of being symptomatic.
- These criteria required the following strategy:
- 20 countries were selected and 100+ sites were needed to expand the net as wide as possible.
- Sites needed to be a mix of emergency rooms, local clinics, and infectious disease units.
- Supporting study awareness was critical.
- In-clinic hospital posters and information packets were imperative to promote top of mind awareness of the study with site staff.
- Doctor to doctor pre-built yet customizable templates were helpful to sites, especially when needing to tap into locally networked sites.
- Local advertising was helpful, but very restricted or even prohibited in some of the countries involved.
- A global site mix that involved both hemispheres to increase the probability of subject capture within the desired project timeline and within the global flu seasons (different by hemisphere) to maximize subject throughput potential.
- Converting patients to subjects within the inclusion window required providing sites with rapid diagnostic Influenza A test kits to support rapid diagnosis confirmation and appropriate triage or referral to study centers. These test kits allowed the sites to make a positive diagnosis of Influenza A in as little as fifteen minutes.
ADDITIONAL CHALLENGES ENCOUNTERED
- A weak flu season in the southern hemisphere
- The 2017 - 2018 Influenza A flu season was light compared to other flu seasons. Most of the infected patients in the southern hemisphere had a mild variant, so patients meeting the criteria of hospitalization and oxygen therapy were harder to find. This increased the importance of a bi-hemisphere site approach.
- Being ready for flu season
- This study ran into this issue and pushed First Patient In (FPI) into the later part of the 2018 season with FPI being achieved in January.
- With government funding involved, it can take time for the funds to be allocated and IP to be ready for shipment.
- The timing of securing funds cannot be dictated by sponsors seeking government funding, but it's important to note the impact it can have on patient enrollment and study execution.
- Importing equipment to sites
- This takes additional time and adds complexity to start. Always ensure you leave time for this in your project timeline as navigating site requirements as well as country level requirements for importation is time-consuming.
- We supplied the rapid diagnostic Influenza A test kits and additional equipment relating to the IP needed for treatment.
LESSONS LEARNED OF VALUE
- Depending on patient inclusion criteria specificity and influenza seasonality, your Influenza A clinical trial may benefit from a bi-hemisphere approach.
- Keeping your study top-of-mind and supporting awareness of an influenza study is vital, especially when it requires patient referral as an integral dynamic of study enrollment.
- Be ready to support FPI at the beginning of the flu season. A great rule of thumb is to give yourself 6 months from FPI, especially if a global study. This way you maximize your total subject recruitment months with the most sites available/active by the intended FPI date.
- When importing equipment to sites/countries, always give yourself a buffer for the unexpected in your timeline.
HELPFUL RESOURCES FOR YOUR NEXT STUDY
- The World Health Organizations Influenza Surveillance Monitoring page.
- Weekly updates on geographic influenza spread (HERE)
- Summary reviews of influenza seasons by hemisphere (HERE)
- You can be notified of updates to their page by sending an email to email@example.com
Example of WHO Weekly Update
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