Real-Life Examples of Studies Hurt by Drug Shortages and Tips to Avoid
Final installment in a three-part series on drug supply shortages in clinical trials with BioClinica's Trident IRT Team.
If you've been following this blog series on drug shortages, you know why it's so important to stay on top of clinical trial drug supply and the potential impact on clinical trials when shortages do occur: subject loss, lowered enrollment, budget escalation, delays and even study discontinuation.
In this post, we'll look at three real-life examples where BioClinica was requested eleventh-hour to help out where drug shortages put studies on a collision course with disaster.
Study 1: Chronically Low Supplies Affect Open-Label, Single Country Study
This clinical trial was experiencing chronically low drug supply. Some sites had resorted to assigning kits at their own discretion rather than using their IRT in combination with ongoing reconciliation.
Additionally, several sites were splitting kits between subjects, providing extra kits, and/or not tracking what was being handed out. Consequently there has been insufficient supply to meet expected enrollment, leading to the loss of several subjects to date.
The root causes of drug supply shortages in this study were a combination of factors:
- Incorrect initial expectation of enrollment rates. This led to depletion of original manufactured lots sooner than expected.
- Poor communication among the sponsor, CRO, and depot about when resupplies would be available.
- Operating in a reactive vs. proactive mode with site resupply settings. Resupply values were not adjusted to account for high enrolling sites.
This study is continuing – but supplies are being monitored as closely as feasible given the situation. As the study is winding down, the ability to take additional actions are limited at this point.
The consequences of chronic drug shortage in this trial are quite ominous. Because of manual kit dispensing, the IRT is unable to accurately predict inventory needs. The system is reliant on manual orders placed by the CRO and are based on site feedback.
Supply reconciliation is ongoing; however data is quickly outdated as some sites are less responsive in supplying the requested information. The use of an automated clinical trial supply management tool like Optimizer would have been a tremendous benefit to this study.
Study 2: Early Packaging Vendor Issues Threaten Double-Blind Global Trial
In this study the packaging company was unable to meet original supply expectations, delaying the initial packaging run. Drug shortage early on led to manual site monitoring and resupply order processing, driving up shipping costs. Manual kit substitution was done in an attempt to avoid subject loss.
The situation was further complicated because the study team underestimated overage expectations for initial site supply. Compounding the situation, some of the original batches of drug were rejected, further reducing available supply.
Capacity constraints have caused the packaging company to continue to lag behind study demand. Unfortunately, there is no unblinded supplies person available on the study team to review data and forecast and manage supply needs.
As a remedy, BioClinica is using clinical trial supply software to do unblinded monitoring of supplies at the site vs. upcoming patient visits. Manual kit substitutions are being done in an effort to prevent subject loss. This requires personal contact with the IRT team for each dispensing.
New demand expectations have been reset with the packaging company.
Study 3: Enrollment Issues Become Pronounced in Double Blind Global Trial
In this study, the Sponsor had insufficient supplies due to a mismatch in original planning vs. actual enrollment rates. To remedy the problem, an unblinded team is doing manual monitoring of shipments. Protocol windows are being strictly enforced in an effort to ensure supplies are on site when needed.
The Sponsor had initiated its own work-around in an attempt to correct supply delivery timing. Sites were instructed to allow a minimum amount of time prior to enrollment vs. protocol. This unfortunately led to more “urgent” orders being processed via the depot ─ and at additional cost.
The root cause of this undesirable situation can be traced to original planning. A lack of understanding surrounding batch sizes and manufacturing timelines worsened supply problems. Earlier and more thorough planning could have minimized or completely avoided these supply issues.
More Great Tips to Avoid Shortages
Some difficult situations indeed!
To help avoid drug shortages in your own trials, here's some more great advice from our experienced IRT team in addition to the tips provided in my earlier blog.
- Closely monitor enrollment at all of your locations, especially actuals vs. expectations. Set up alerts when country-specific supplies are low. Allow time to react and account for packaging and shipping timelines.
- Actively keep an eye on all supplies. In the event enrollment is happening quicker than anticipated and at more varied locations, be mindful of the overall impact on study sites.
- Monitor your "Do Not Count" / "Do Not Ship" to help ensure sites are resupplied in time. Use early warning alerts to stay aware of dates surrounding expiry. Have measures in place that allow you to either update expiry or obtain replacement supplies.
- Identify where potential risks are and lay the groundwork for a smoother running study over the long-term. For instance, limiting site enrollment in select countries may make sense in certain situations.
- Carefully consider the length of time supplies are kept in the main depot to account for country-to-country issues.
- Maintain clear and continuous communication with the many different stakeholder groups throughout every study phase.
While these are just a few quick pointers, I hope you picked up something new to apply to your own studies.
Drop us a line and share what's working (or not working) for you. If you'd like to see a demo of BioClinica's Trident IRT or Optimizer clinical trial supply management solution, call us at 1-888-392-7456. We'd love to hear from you.