Introduction
Clinical trial rescues can often be a delicate topic for both sponsor and contract research organization. When a study goes off track, it’s natural to want to point fingers and look for who is to blame. However, performing a comprehensive root cause analysis and managing expectations and communication from the start will allow sponsors to move forward with the study and develop a successful plan for getting the trial back on course, instead of getting bogged down in assigning fault. The costs associated with missed milestones and timeline extensions are significant and can derail the trial entirely. Less than 10% of drug candidates reach approval, with sponsors often incurring the costs associated with failed clinical trials, or trials that are behind schedule. Playing the “blame-game” while a clinical trial fails will only slow down the rescue process and increase these costs. It is paramount that sponsors and CROs are proactively monitoring trial progress and working together to address issues as they arise.
When is Rescue Needed?
Studies may fail to meet time, cost or quality expectations for a myriad of reasons. Operational failures may occur if the study is lacking in planning, oversight and communication between the sponsor and the CRO. These are highly related to issues with time, cost or quality in a faltering study. CROs are responsible for balancing the budget and timeline requests of the sponsor with the realistic challenges and unpredictable nature of running clinical trials. Therefore, they must present a clear plan from the start with contingencies for achieving key milestones despite any bumps in the road. This should involve continuous monitoring of trial progress rather than scheduled, intermittent monitoring and establishing a clear response plan for addressing any concerns with the study.
Often, the blame-game occurs when expectations between the sponsor and the CRO are not discussed fully at the inception of the trial. Failure to set realistic goals and clearly establish responsibilities can lead to finger-pointing between the sponsor and its partners when a clinical trial goes awry. When CROs overpromise on meeting budget and timeline expectations of the sponsor without sufficiently considering the challenges, they are setting up for failure or disappointment in later stages of the clinical trial. All parties must candidly discuss the risks and clearly define roles in mitigating any issues that arise. This can help avoid operational failures due to lack of planning and improper oversight or response. Proper communication also involves engaging in discussion with the study sites. The CRO should encourage active participation by the sites to address enrollment challenges and to offer additional support and training when needed. Sites can offer valuable information regarding difficulties enrolling patients or maintaining adherence, which can inform decision-making between the sponsor and the CRO on how to proceed with the rescue.
Figuring out the “Why”
Each trial faces unique challenges that must be addressed through diligent project management and proactive monitoring of study progression by both the sponsor and the CRO. Key performance indicators (KPIs) should be established from the start and analyzed throughout the trial to identify areas that are not meeting expectations. KPIs should be comprehensive and consider factors such as recruitment, data quality, and compliance. Prior to intervening, a thorough root cause analysis should be performed to diagnose the faltering study and understand why the trial is not meeting milestones. The root cause analysis must consider the process and protocol, as well as relationships between the sponsor, CRO and sites. This method allows sponsors to identify areas requiring additional oversight or modified response procedures. What it shouldn’t do is turn an already bad situation into a he said/she said.
Tools such as Biorasi’s Study Checkup can be employed to identify areas of concern and evaluate overall study health based on the timeline, budget expectations and the current study performance. The Study Checkup provides a comprehensive analysis of red flags that may arise in enrollment, site activation, budget or regulatory status. Additionally, these areas of concern are prioritized to inform sponsors how to proceed in tackling each. Ultimately, though, the specific assessment you use is less important than the thoroughness of that assessment to identify the specific causes of failure.
Once the root cause has been determined and the areas of concern are clearly established, the sponsor, CRO and sites should work harmoniously to create an intervention plan that addresses the current study concerns and adapts the approach to address prevailing issues. All three parties must make adjustments to adapt to the new intervention plan in a timely manner in order to avoid further delays in the trial.
Planning for the Future
Obviously, a successful trial is better than even the most well-coordinated rescue. Proactive intervention and open lines of communication between the sponsor and its partners are a must to minimize future need for rescue. Sponsors and CROs should remain vigilant in monitoring trial progression and responding to early warning signs of a faltering trial. Quick response can be the difference between completion and failure, and that quick response is entirely dependent on the sponsor and their CRO being able to have open, honest conversations about the health of their trial.
Although it may be difficult to anticipate certain problems ahead of time, periodic reviews of study progress can reveal small issues before they become bigger, more serious problems that interfere with the timeline and budget set out at the start. This can be effective in preventing compounding of issues that become costlier and more damaging to a trial as they are left unresolved. The sponsor can also choose to involve a third-party evaluator to objectively assess areas of concern and identify any needs for improvement.
Eliminating the blame-game in clinical trials is mutually beneficial for not only the sponsor and the CRO but also for individual patients and the health system as a whole. Immediately diagnosing the problem and seeking a solution rather than assigning blame will allow the trial to be reinvigorated at a faster pace and allow the sponsor to deliver a potentially life-saving drug much sooner.
