4 Hidden Gaps In Clinical Trial Preparation For Small Biotechs

By Jessica Cordes, Senior Consultant, Clinical Excellence GmbH

For many small biotechs, the transition into clinical development represents years of scientific work, significant investment, and high expectations. Yet despite strong science and promising early data, some clinical trials fail to meet timelines, struggle with enrollment, or face costly operational disruptions.

The reason is rarely a lack of scientific innovation. More often, failure is embedded in the way the clinical trial was prepared.

Before the first patient is enrolled, critical misalignments between strategy and operational reality can determine the trajectory of a clinical trial. These gaps are not always visible at the executive level, especially in organizations with limited in-house clinical operations experience. However, their consequences are very real, affecting timelines, budgets, data quality, and ultimately the likelihood of regulatory success.

The Disconnect Between Strategic Vision And Operational Execution

In small biotechs, clinical development strategy is often driven by a small leadership team under pressure to move quickly, achieve milestones, and maintain investor confidence. While this is understandable, it often leads to the incorrect assumption that operational execution will follow once the strategy is defined.

Clinical trials, particularly in oncology and advanced therapy medicinal products, such as cell and gene therapies, are highly complex and depend on the coordination of regulatory, clinical, manufacturing, and operational elements. These interdependencies must be considered from the earliest planning stages. When they are not, the result is a trial design that looks viable on paper but is difficult to implement in practice.

For example, regulatory pathways can support accelerated development, but they require early alignment with authorities, well-defined endpoints, and operational readiness across functions. If these elements are not integrated into planning, the advantages of such pathways are lost, and delays become likely. The issue is that strategy and operations are often developed in parallel without sufficient integration.

Gap 1: Overestimating Recruitment Feasibility

Enrollment projections are often based on high-level assumptions about disease prevalence or site promises. However, these assumptions rarely translate into actual enrollment performance. Eligibility criteria, competing clinical trials, site capabilities, and patient pathways all influence whether patients can be identified, screened, and enrolled. For cell and gene therapy clinical trials, this challenge is even more pronounced because patient populations are often small, highly stratified, and difficult to access.

Traditional feasibility approaches, such as site questionnaires or investigator estimates, frequently overstate the true recruitment potential. When recruitment assumptions are unrealistic, the consequences can cascade across the entire trial:

• Timelines extend.
• Costs increase due to prolonged clinical trial duration.
• Operational pressure increases on sites and teams.
• Protocol amendments become more likely.

From an executive perspective, the critical question is how many patients can realistically be enrolled under the specific clinical trial setup. Organizations that address this proactively use data-driven feasibility assessments, integrate site-level experience, and stress-test eligibility criteria early.

Gap 2: Missing Country Feasibility

Country is one of the most important determinants of clinical trial success. Selecting the wrong countries can undermine even the most well-designed protocol. Regulatory timelines, infrastructure readiness, investigator experience, and patient access differ significantly across regions. Without a robust feasibility assessment, companies risk selecting locations that cannot deliver on expectations and therefore run trials subject to delays in regulatory approvals, low recruitment rates, or operational disruptions.

A structured country feasibility analysis allows organizations to:

• identify regulatory timelines and approval variability
• assess competition from other clinical trials
• evaluate country-specific start-up requirements, including ethics review, contract negotiation, site activation, and import or export processes
• determine whether local infrastructure can support the protocol, including diagnostic pathways, treatment capacity, laboratory requirements, imaging access, and specialized procedures
• assess investigator experience with the indication, modality, and expected safety management requirements
• understand reimbursement, standard of care, and patient access differences that may influence enrollment behavior
• optimize budget and timeline assumptions by replacing generic benchmarks with country-specific evidence
• reduce the risk of selecting countries that look attractive strategically but cannot deliver operationally.

In advanced therapies, sites must be able to handle complex logistics, including product handling, cryogenic storage, and interdisciplinary coordination. If these capabilities are not assessed thoroughly during country and site selection, operational failures become almost inevitable.

Gap 3: Lack Of Cross-Functional Alignment

Clinical trials require continuous coordination between clinical operations, regulatory affairs, manufacturing, quality, and external partners. In small companies, these functions are often still developing or operating with limited resources. As a result, alignment is frequently assumed rather than actively managed.

This becomes particularly problematic in complex clinical trials, where timing and coordination are critical. For example, in autologous cell therapy clinical trials, patient scheduling must align with manufacturing capacity and logistics. Delays in any component can lead to missed treatment windows and loss of product.

From a strategic perspective, cross-functional alignment becomes a risk management function. Leadership must ensure that all stakeholders are aligned on timelines, responsibilities, and decision-making processes before the clinical trial begins.

This requires:

• clearly defined governance structures with documentation
• integrated planning across functions
• transparent communication channels
• defined escalation pathways.

Gap 4: Underdeveloped Training And Operational Readiness

Training is often underestimated in early clinical planning, especially in organizations moving into first-in-human or early-phase clinical trials. General GCP training is rarely sufficient for complex clinical trials, particularly those involving cell and gene therapies. These require specialized knowledge related to product handling, administration, safety management, and long-term follow-up.

If site staff and operational teams are not adequately trained, trials will be subject to:

• protocol deviation increases
• data quality decreases
• patient safety risks
• longer trial timelines.

Training must be tailored not only to the protocol but also to the specific function of the involved stakeholders. Site staff, manufacturing teams, logistics providers, and sponsors all require different levels and types of training. It also must be continuously updated as protocols evolve, new sites are added, and new risks are identified.

The Compounding Effect Of Early Gaps

Each of these gaps presents a significant risk. However, they rarely occur in isolation and can create a situation where the trial struggles from the outset. By the time these issues become visible during clinical trial execution, corrective actions are limited, costly, and often too late to fully mitigate the impact. This is why the most effective clinical strategies focus not only on what needs to be done but also on whether it can be done under real-world conditions.

A Strategic Shift: From Planning To Operational Reality

Clinical development planning must incorporate operational feasibility as a core strategic component. This does not mean slowing down development but making more informed decisions earlier.

Executives should ask themselves:

• Are recruitment assumptions based on validated data?
• Does country selection align with regulatory timelines and infrastructure readiness?
• Are all functions aligned on clinical trial execution requirements?
• Is the training strategy sufficient for the complexity of the clinical trial?

Executives and organizations that adopt this approach are better positioned to meet timelines, manage risks, and generate high-quality data.

The Role Of Leadership In Preventing Failure

Executives set the priorities, define the level of rigor applied to planning, and allocate resources to critical areas such as feasibility, training, and cross-functional integration. In small biotechs, where resources are limited and timelines are tight, these decisions are particularly important.

Strong leadership in this context means:

• recognizing the importance of operational expertise
• challenging assumptions in early planning
• investing in the right processes and capabilities
• creating an environment where risks are identified and addressed early.

Success Is Determined Before First Patient In

For small biotech companies, where margins for error are limited, addressing gaps early can make the difference between success and failure. By aligning strategy with operational reality, leadership teams can create a foundation for clinical trials that are scientifically sound and reliably executable.

About The Author:

Jessica Cordes is a clinical operations expert and founder of Clinical Excellence GmbH with more than 15 years of experience planning, governing, and executing international clinical trials, with a focus on oncology and cell and gene therapies. She supports small biotech sponsors in building practical, GCP-compliant structures for clinical trial planning, start-up, sponsor oversight, vendor management, risk management, and operational decision-making. The benchmark report “Global Clinical Trial Approval and Setup Timelines” reflects her focus on translating regulatory requirements into usable planning guidance for global clinical trial teams. Since 2023, Jessica has worked as an independent consultant and trainer and provides GCP training, templates, and practical implementation support through the Clinical Excellence Training Academy.