Trial Complexity: A Study from the Boston Consulting Group
The past decade has seen substantial innovation in clinical trials, including new trial formats, endpoints, and others. There have been regulatory changes, increasing competitive pressures and other external factors which impact clinical trials.
In parallel, trial timelines have increased and success rates remain stubbornly low. This has led many observers to question whether clinical trials have become overly complex and if this complexity is always needed. The Boston Consulting Group presents a large-scale analysis of protocols and other data from over 16,000 trials.
Using a machine learning algorithm, they automatically assessed key features of these trials, such as number of endpoints, number of inclusion–exclusion criteria and others. Using a regression analysis they combined these features into a new metric, the Trial Complexity Score, which correlates with overall clinical trial duration.
Looking at this score across different clinical phases and therapeutic areas they saw substantial increases over time, suggesting that clinical trials are indeed becoming more complex. They discuss drivers of increasing trial complexity, necessary or helpful (‘good’) complexity versus unnecessary (‘bad’) complexity, and explore mechanisms of how sponsors of clinical trials can reduce trial complexity where appropriate.
Analysing Trial Complexity Scores by therapy area (TA) shows increases across all TAs.
Oncology has historically had the most complex trials, including in major indications such as prostate, colorectal, breast and lung cancer. Between 2014 and 2020, the average complexity of oncology trials was increasing steadily, but has levelled off since 2020. They believe this may be due to the impact of COVID-19 on trial planning.
Immunology and neurology/CNS trials have historically had average trial complexity, with Crohn’s disease, multiple sclerosis and stroke contributing to more complex trials, and spikes being driven by changes in sponsors and modalities. Cardiovascular trials have seen large increases in complexity up until 2021, driven by a surge in endpoints as wearable devices became widely adopted.
Endocrinology has historically had the lowest complexity, but this has been steadily rising over the last few years, driven by moving from lower complexity indications such as diabetes, to higher complexity indications such as NASH. As with cardiology, there is a rise in digital endpoints as a contributory factor.
In and of itself, trial complexity—as defined by our score—is neither good nor bad. There are often legitimate reasons for higher complexity trials, such as the need to address specific unmet medical needs, to ensure rigorous trial design, to address regulatory requirements, or the desire to explore novel scientific objectives. However in some cases complexity may be unnecessary, for example when measuring similar or the same endpoints in different ways; or having an excessive number of exploratory endpoints.
Whatever the reason for trial complexity, it can be associated with increased burdens on patients and investigators, higher costs, and—as this analysis demonstrates—longer timelines to bring medicines to patients. However the analysis also shows that clinical trial complexity is not inevitable, as low-complexity trials exist in every disease area, and for all major indications the spectrum of trial complexities is extremely wide. It is therefore worth examining carefully whether complexity can be reduced in a given trial.
Effective strategies to lower trial complexity usually start with systematic evaluation of complexity at the protocol or synopsis review stages. Oftentimes trial design does not take into account the impact on patient and investigator burden, and does not always sharply focus on what is sufficient for approval and competitive market access. Throughout the trial design process, complexity should be assessed regularly to ensure the trial complexity remains under control. In governance forums, trial complexity can be a useful dimension to support decision making about planned trials.
In conclusion, the Boston Consulting Group’s analysis demonstrates that clinical trial complexity has increased across all phases and most therapy areas. This has many consequences, specifically longer timelines to bring medicines to patients, a higher likelihood of protocol changes, higher patient and investigator burdens, increased chances of errors and biases, alongside potential replication challenges. Going forward, sponsors will need to decide if the increases in trial complexity are truly required (e.g. to demonstrate an important outcome or endpoint), whether the consequences of greater complexities are worth it, and how to navigate the cost/speed-versus-complexity trade-off.
How Simplified Trial Processes Can Increase Participation
Clinical trials are the foundation of medical progress and allow researchers to test and refine treatments. Participation in these studies often falls short of expectations due to complicated enrolment processes, overwhelming procedures, and logistical barriers. Simplified medical trials make the process more accessible and patient-friendly. They encourage participation but also improve retention, which produces reliable, meaningful data.
Simplification begins with understanding the perspective of potential participants. What challenges do they face, and how can these be mitigated? Trials that prioritise accessibility, communication, and convenience create an environment of engagement and trust.
Improving Access with Streamlined Processes
Accessibility is one of the most significant factors in patient participation. Many potential participants aren’t able to join trials because they live far from study sites, have mobility challenges, or can’t take time off work. Simplified processes directly address these barriers with a more inclusive approach to research.
Technology expands access through remote consultations, virtual check-ins, and online consent forms so participants can engage in trials without the need for frequent travel. This particularly benefits patients in rural areas or those with limited transportation options. Virtual participation removes geographic location as a limiting factor.
Trials improve accessibility by simplifying how information is presented. Complex medical jargon and lengthy consent documents can intimidate potential participants, while clear, concise explanations and visual aids help individuals understand what is involved.
Financial and logistical support further remove barriers. Travel expense reimbursements, home visits, or flexible appointments make participation feasible for more patients. These small changes increase patient participation through a commitment to patient-centred care.
Simplified Medical Trials Build Trust and Confidence
Successful clinical trials are based on trust. Patients will participate and remain engaged when they feel confident in the safety, transparency, and purpose of the study. Simplified medical trials build this trust by focusing on clarity and patient well-being.
Educational materials play an important role in building confidence. Plain language helps participants fully understand the study’s goals, potential risks, and expected outcomes. Informed patients develop a sense of ownership and commitment to the trial.
Open communication channels strengthen trust. Researchers can create a supportive environment and reduce dropout rates by giving participants regular trial progress updates, access to medical staff, and prompt responses to their concerns.
Safety is another factor. Streamlined protocols prioritise patient well-being, reduce the risk of complications, and reinforce confidence in the process. Trials that have a clear focus on participant health and safety build long-term trust in the research community.
Making Trials Convenient and Patient-Focused
Convenience is one of the most important aspects of increasing patient participation. Patients juggle work, family, and other commitments, and don’t have much time to dedicate to a trial. A simplified trial process makes a difference for these individuals.
Remote monitoring tools and wearable devices are ways that convenience can be integrated into trials. These tools allow participants to provide data from home and reduce the need for frequent clinic visits. A wearable device can track vital signs or medication adherence and send data directly to researchers. This saves time and reduces the burden on participants.
Flexible scheduling is another factor. Trials that allow participants to choose appointment times or complete certain tasks at their convenience demonstrate respect for their commitments. Home-based services like sample collection or telemedicine consultations further ease the burden of participation.
Streamlined data collection increases convenience. Participants feel less overwhelmed when the amount of paperwork and redundant forms are reduced or eliminated. The focus on simplicity creates a positive experience that encourages both enrolment and retention.
Patient feedback helps improve convenience. A commitment to continuous improvement inspires trust and participation and is demonstrated by listening to patients’ experiences and adapting trial processes accordingly.
Keith Berelowitz | Founder & CEO
Keith Berelowitz is the Founder of pRxEngage, a company redefining patient engagement and retention in clinical trials using living experience, proven methods, and AI.
