How Clario is improving clinical trials: 'Therapies that hold immense promise may never see the light of day'
We caught up with Dr. O’Neal to discuss the telltale signs of trouble in clinical trials that sponsors can pick up on early and how they can address these issues swiftly to keep their trials on track and effective drugs within reach for patients.
BPR: What are common challenges drug developers face during clinical trials?
During clinical trials, drug developers often face operational and data-related challenges that can significantly impact whether trials are successful. Drug development is incredibly complex, particularly in late-stage clinical trials in areas such as oncology, musculoskeletal disease, and Alzheimer’s, where imaging is heavily relied on and creates additional layers of complexity. Challenges include flawed study designs, inadequate endpoints, low-quality data, and poor site management, leading to increased costs and barriers to patients receiving access to these promising and potentially life-saving therapies.
BPR: How do these challenges impact the likelihood of achieving regulatory approval?
These operational, data management, and image acquisition challenges put many promising therapies at risk of never receiving regulatory approval, as drug efficacy alone is not always an accurate predictor of success in clinical trials. Ninety percent of drug candidates fail during clinical trials, which cannot always be attributed to a lack of efficacy; some therapies that hold immense promise for patients may never see the light of day. Recurring problems like inconsistent assessments of data or imaging can cause headaches for drug developers and contract research organizations (CROs) and exacerbate other issues like high adjudication rates and site-central discordance, decreasing the likelihood of regulatory approval.
BPR: What strategies can drug developers deploy to address these challenges and keep clinical trials on track?
Drug developers, sponsors, and CROs can identify and address warning signs of potential trial issues early if they know what to look out for. Incomplete data, image acquisition issues, and missed timelines are problems that should raise immediate red flags for sponsors to investigate and determine where intervention is needed. These problems often appear at the site level, and delayed or incomplete imaging assessments, training issues due to limited site familiarity with the protocol and limited familiarity with read paradigms. resulting in downstream problems. An urgent and proactive focus on making practical enhancements is needed, such as obtaining high-quality images from CT, MRI, and PET scans in a consistent manner and training personnel to perform objective assessments to ensure data integrity is not compromised. Occasionally, these problems may force drug developers to look for additional strategies or partners to course-correct and salvage their research to meet regulatory requirements and timelines, minimize financial losses, and make these therapies accessible to patients.
BPR: Can you define what rescue studies are in clinical trials and when drug developers should consider?
Rescue studies are clinical trials transferred from one vendor to another to ensure the integrity of the trial and achieve regulatory approval. Studies that require “rescuing” often experience issues with questionable data quality and integrity, missed regulatory deadlines, and poor project management that introduce many barriers to achieving regulatory approval and commercial success. The decision to rescue a study is difficult but often necessary for getting clinical trials back on track and can sometimes be the best and only chance of the drug reaching patients. Poor site management and the mismanagement or misallocation of resources may cause too many delays that may put drug developers in a race against time to find another partner that can deliver on the study charter and improve prospects for approval.
BPR: What challenges or problems do rescue studies face?
Rescue studies come with their own unique transition challenges, requiring proactiveness and clear communication from all parties for the initial transition process to run smoothly. Challenges can appear in the collection and de-identification of data when transitioning all historical data, as well as training and qualifying new sites or personnel. The data transition process must be thorough and reviewed by clinical experts who can help ensure high-quality imaging data and reasonable adjudication rates while providing insights to overcome or avoid surprises. This can be an error-prone process given the highly technical, arduous nature of transitioning studies from one vendor to the next, making it critical to co-develop a transition plan and establish clear communication channels.
BPR: What are successful strategies for overcoming these challenges and successfully rescuing clinical trials?
Collaboration, experience, technology, and training are integral to building a foundation for a successful rescue study, requiring sponsors and partners to work closely together to align on expectations and minimize delays as the trial picks up and deadlines are on the horizon. Proactive project management is essential for eliminating risk and reducing further delays by accelerating user and site training and bringing stakeholders together to meet study-specific requirements.
Comprehensive reader training and experience are also important to meet aggressive timelines and gain alignment on handling specific scenarios to enable optimal reader quality and minimize discordance. Robust personnel qualification and training are crucial for extracting actionable insights and data, which helps predict performance and achieve acceptable adjudication rates. Additionally, this training can improve image submission and data management for greater data quality and control.
Most importantly, a dedicated team with rescue study experience and well-defined processes is critical to start the transfer process quickly and efficiently for positive results.
