Trials of the century

Overcoming operational hurdles and igniting clinical trials

Drug efficacy isn’t always a predictor of success for clinical trials. Many trials have been deemed ‘failures’ or ‘unsuccessful’ even when these therapies’ mechanisms of action are clinically sound.

Too often, trials are plagued by flawed study designs, inappropriate endpoints, low-quality data, poor site management and mismanagement or misallocation of resources, causing delays and putting drug developers and contract research organisations (CROs) into a race against time to salvage the research, meet deadlines and minimise financial losses.

These factors and their impacts are exacerbated in late-stage clinical trials, particularly where imaging is the primary endpoint, for example in oncology, musculoskeletal disease, or Alzheimer’s disease. It can be challenging to obtain consistently high-quality images from CT, MRI and PET scans, as well as clinical experts with the qualifications and experience to perform objective assessments.

These issues can lead to problematic read paradigms and high adjudication rates that may contribute to a drug not receiving regulatory approval.

There are often early warning signs of trouble that, if addressed early, can keep trials on track. Often, red flags arise at the site level, such as missing data, blown timelines, or image acquisition quality issues that can be attributed to insufficient training.

Other times, issues stem from questionable reader quality and paradigms, and, in either case, data integrity is compromised and must be addressed swiftly to avoid downstream issues.

Navigating these challenges and correcting the root causes requires a proactive, strategic approach. This may trigger the decision by sponsors to rescue, or transition, their study to another partner who can deliver on the study charter and improve the likelihood of regulatory approval.

The decision to trigger a rescue study is difficult and requires additional investment upfront, but it’s often necessary to ensure the integrity of the trial and, most importantly, that a drug has the best chance of reaching patients in need.

Triggering a rescue study does not come without significant transition challenges, as all historical data must be appropriately collected and accounted for, and new clinical experts must be promptly brought into the fold.

A thorough data transition process is as critical to success as the trial’s continuation with high-quality imaging data, a reasonable adjudication rate and relevant experience to navigate the inevitable complexities of a rescue study.

A successful rescue study hinges on several factors, including experience, technology, training and collaboration between the sponsor and vendor, to ensure clinical trials get back on track efficiently and effectively.

As a first step, clear lines of communication and the co-development of a thorough transition plan are critical for ensuring all involved parties have what they need to proceed and align on expectations.

From beginning to end, rescue studies rely on proactive project management of strict deadlines and collaborative workflows with sponsors to eliminate risk and reduce further delays.

Strong project management can accelerate proper site and user training, as well as ensure that the principal investigator, nurses, medical writers, participants and other stakeholders are all working together to meet study requirements.

Additionally, experience is pivotal in using historical data to predict data trends, adjudication rates, and reader performance within specific indications and read paradigms to get trials back on track with transparency top of mind.

This experience must also be combined with an extensive reader network ready to engage in order to meet aggressive timelines. Comprehensive reader training is necessary to gain alignment on how specific scenarios may be handled to ensure optimal reader quality and minimise discordance.

This level of personnel qualification and training delivers value in the form of robust data and insights that can be leveraged to optimise the trial going forward. For example, it’s possible to predict reader performance at tumour-specific levels and equip sponsors with a degree of certainty regarding discordance and adjudication rates.

Furthermore, image submission and data management technology are vital for data quality control and can help facilitate reader coordination from anywhere in the world.

The ability to efficiently allocate cases to the reader network optimises productivity, enabling stakeholders to meet tight turnaround times that keep the rescue study on track.

There is no one-size-fits-all approach to navigating the complexities of clinical trials or rescue studies, but experience plays a pivotal role.

While rescue studies are disruptive by nature, the combined decision to rescue and select a credible partner may be the best path forward to increasing the likelihood of long-term success.

One thing is clear: operational failure should not be what holds back drugs with compelling promise, especially for patients who need them the most.