The landscape of clinical trials is undergoing a transformation marked by increasing intricacy and operational challenges. Ken Getz, Executive Director and Research Professor at Tufts CSDD, presented a thorough analysis at the 2024 SCOPE Summit, unraveling trends that spotlight the complexities and evolving dynamics in the clinical trials industry.
Design and Executional Customization
Getz outlined the alarming escalation in trial protocol variables from 2010 to 2020. The Tufts CSDD study, covering several thousand protocols, indicated a near doubling of endpoints and a tripling of data points collected. This heightened complexity is inversely related to trial performance, with longer cycle times, increased amendments, and higher dropout rates being the dire consequences. Getz also elaborated on the increasing clinical trial execution fragmentation; for example, from the year 2000 to 2020, CRO and tech vendor service costs increased from $10.4 bn to $78.6 bn, respectively, while investigative site costs increased from $5.9 bn to $15.3 bn.
A Closer Look at Pivotal Trial Designs and Their Performance
Getz pointed out that pivotal trials have become considerably more intricate in the Tufts CSDD studies. The total endpoints nearly doubled over the past decade, and the number of procedures has escalated by 40.6%. Interestingly, the number of eligibility criteria was reduced by 11.8%, possibly indicating a shift towards broader participant inclusion in some aspects of clinical trials. The total number of investigative sites increased by 60.1%, expanding the geographical and logistical scope of trials.
However, this complexity seems to hamper clinical trial performance. From 2010 to 2020, the duration from protocol approval to the first patient’s first visit increased by 27.2%, and the enrollment duration from first patient first visit to last patient last visit rose by 36.9%. These changes coincide with a dramatic spike in substantial amendments (113.3%) and dropout rates (105.1%), supporting Getz’s point about complexity’s inverse relationship with performance.
Surge in Substantial Protocol Amendments
In his detailed examination, Getz highlighted a concerning trend in clinical trial management as evidenced by the rising number of substantial protocol amendments. The Tufts CSDD research revealed a sharp increase in such amendments, particularly in Phase III trials. The data illustrates that between 2018-2021, there was a notable escalation in the percentage of protocols with at least one substantial amendment in Phase III trials to 82%, up from 66% in 2013-2015. This rise is mirrored by an increase in the mean number of substantial amendments per protocol, jumping from 2.3 to 3.5 in the same period. Getz’s analysis points toward a reactionary approach in clinical trial management, where amendments, while necessary to address unforeseen issues, introduce significant disruptions and add to the complexity and cost of trials.
Declining Site Activation Rates
The presentation also shed light on investigative sites, particularly the declining activation rates, which have significant implications for clinical trial efficiency, particularly in North America, where rates have plummeted to 62%. “What this suggests is that 40% of sites in North America that we actually will look to engage will not activate. Some of those sites may never get through the contracting and budgeting process. They may never get approval from the IRB and a percentage of those will have difficulty actually enrolling a single patient as well,” said Getz. These factors collectively contribute to the underutilization of sites and inflated operational burdens. Getz’s findings advocate for a strategic re-evaluation in selecting and managing sites, emphasizing the need to streamline the trial initiation process and minimize protocol complexity to enhance site activation and participation rates.
Volunteer Participation Experience and Demographic Disparities
Addressing another grave concern, the research highlighted the demographic disparities in trial participation. Black or African descent populations are highly underrepresented in trials, with only a third of the necessary population being recruited for proportional representation. This disparity is attributed partly to the complexity and location of the trials, affecting convenience and access. Additionally, the data presented by Getz highlighted the challenges faced by clinical trial volunteers, with protocol adherence being a significant issue, as Phase III trials saw the highest proportion of patients with protocol deviations. Getz also emphasized the importance of patient feedback, frequently pointing out the excessive time commitment and cumbersome procedures as significant drawbacks.
Site and Patient Perceptions of DCTs
Decentralized Clinical Trials (DCTs) present a nuanced landscape of acceptance, as outlined by Getz. Most ethnic groups consider having ‘options’ for DCTs important, with most patients feeling more comfortable with telemedicine, smartphone apps, wearable devices, and home visits. Yet, concerns are notable; 43% of Hispanic/Latino participants fear additional costs, and over half of the participants worry about privacy and the impact on their relationships with study staff due to DCTs.
On the site front, perceptions are mixed. While 61.4% of sites prefer hybrid or full DCT models, they also report substantial increases in perceived change in burden. Sites face over 25% more burden in patient education and learning new technologies. Moreover, they note nearly a 20% increase in adverse event monitoring and reporting burden. However, they also report a nearly 15% decrease in patient recruitment and retention burdens.
This duality highlights the critical need for careful consideration when deploying DCTs. Sites and patients recognize the benefits of DCTs but also caution against their challenges. The industry must address cost concerns, privacy issues, and increased workloads to align DCTs with patients’ and sites’ needs and capabilities.
Summary: A Call for Actionable Change
The insights provided by Getz’s Tufts CSDD research at the 2024 SCOPE Summit paint a picture of a clinical trial landscape at a crossroads. The pronounced rise in protocol complexity and associated costs, diminishing site activation rates, and pervasive demographic disparities signal an urgent call to action. The clinical trial ecosystem must navigate these challenges with strategic finesse, optimizing protocols to balance the thoroughness of data against the agility and inclusiveness of trials. As the industry moves forward, it’s imperative to leverage these insights to foster innovation in trial design, management, and execution, ensuring that clinical trials remain robust in their scientific pursuit and responsive to the needs of participants and stakeholders alike.
Moe Alsumidaie is Chief Editor of The Clinical Trial Vanguard. Moe holds decades of experience in the clinical trials industry. Moe also serves as Head of Research at CliniBiz and Chief Data Scientist at Annex Clinical Corporation.
