Protocol complexity has kept increasing for more than a decade, and the operational burden on sites has grown with it.
A piece of important data from SCRS came back recently in yet another LinkedIn discussion: 24% of sites, in one survey, reported turning down trials because they were too complex to execute. While that specific survey is not publicly detailed, it aligns with a large body of evidence showing a steep rise in procedures, data volume, and amendments; and a growing reluctance among sites to take on studies that no longer add up operationally or financially.
The Data Behind the Trend
Multiple analyses from Tufts CSDD, TransCelerate, and global site surveys confirm the scale of the challenge.
Phase II/III protocols now involve around 263 procedures per patient, a 44% increase since 2009.
Phase III trials generate nearly six million data points on average, far more than most sites can realistically process within normal staffing levels.
Protocol amendments have grown sharply: 76% of protocols now include at least one amendment, with a mean of 3.3 per study.
In WCG’s 2024 Site Challenges Report, 70% of sites said trials are “much more difficult to manage” than just five years ago, and complexity is now their number-one challenge.
This is the reality of the moment. Each new procedure, each system login, each amendment translates into cost, time, and pressure on already overstretched teams.
Why Sites Are Saying “No”
1. The economics no longer work.
More procedures require more staffing, more coordination, more documentation, and more technology friction but compensation does not always scale with burden.
For smaller or mid-sized sites, high-complexity studies often consume disproportionate resources for marginal financial return.
Add to that payment terms and delays that impact small and medium operations the most, and it becomes a net loss for work done well.
2. Operational and compliance risk rises.
Complex protocols are fragile: more endpoints, visits, and assessments mean more opportunities for deviations, missing data, or error. With staff already stretched thin, sites rightly worry about audit readiness and quality metrics.
3. Workforce fatigue has become a limiting factor.
Escalating documentation, multi-system workflows, and amendment-driven rework all contribute to burnout.
With many individuals and departments reporting workload overwhelm, increased turnover, protecting staff is now a strategic necessity, not a soft concern.
The Industry Impact
As complexity outpaces feasibility, the consequences ripple through the ecosystem:
Recruitment slows as eligibility criteria tighten and visit schedules intensify.
Dropout increases, driven by participant burden and staff overload.
Only the best-resourced sites can take on certain studies, reducing geographic access and diversity.
A significant portion of the data collected may add little value to primary outcomes, meaning the industry is paying heavily for marginal insight.
Fewer sites = fewer patients = less diversity = often poor if not failed recruitment, trials, and outcomes.
What Sponsors and CROs Can Do
Design for feasibility, not aspiration.
Applying structured complexity assessment tools early exposes the operational burden before protocol finalisation. Every procedure should be justified as core, supportive, or exploratory; low-value, high-burden elements should be reconsidered.
Involve sites early and meaningfully.
Diverse sites, large and small, urban and regional, should shape feasibility reviews.
Ask them directly: What would make this unworkable?
Their feedback is often the fastest route to eliminating unnecessary complexity.
Reduce amendment risk.
Cross-functional review loops, scenario testing, and clearer governance help reduce amendments, one of the major drivers of site overload. If amendments are necessary, prepare and provide pre-worked - and adapted - summaries and explanations.
Align budgets with true burden.
If complexity cannot be reduced, compensation must reflect the time, systems, and coordination required. Complexity-indexed start-up fees and milestone payments are increasingly used to address this.
Also, do ensure payments that do align with site needs/terms, not your own, "standard", terms.
What Sites Can Do
Create a structured go/no-go framework.
Score each protocol on feasibility, workload, systems burden, and amendment risk. Establish thresholds that protect your workforce and quality standards.
Negotiate based on data.
Provide concrete, operationally grounded feedback. Sponsors are far more receptive to well-evidenced requests than ever before.
Simplify internal workflows.
Even complex studies become more manageable when documentation is clear. Tools that transform dense protocols into plain-language synopses and role-specific guidance reduce cognitive load, rework, and onboarding time.
Leveraging Technology and Tools (Including Clinials)
While technology alone cannot eliminate protocol complexity (it's not a magic wand), it can help reduce the operational friction it creates. Sites consistently report that one of their highest burdens is not the science itself, but the volume of documents, systems, and rework required to stay aligned with protocol expectations.
Platforms that centralize information, simplify documentation, and reduce re-reading time are becoming essential. Tools such as Clinials help teams turn dense protocols, amendments, and other trial documents into clear, plain-language synopses and structured content that can be used immediately. This supports faster onboarding, fewer errors, and smoother adaptation when versions change.
Document simplification and leveraging technological solutions will not solve complexity but it does make it far more manageable, sustainable, and less dependent on scarce staff bandwidth.
A More Honest Conversation
The industry now faces a pivotal moment. Complexity has reached a point where feasibility is no longer guaranteed and where sites are increasingly forced to choose sustainability over participation. With a direct impact on trial outcomes.
A new, potentially life-saving treatment should not be held back by trial failure due to lack of sites or patient recruitment not hitting targets. The resources are there, it's about ensuring everything - and everybody - can work together to enable success.
This is not about reducing scientific ambition. It is about precision: collecting what truly matters, designing protocols that can be executed reliably, and building an ecosystem where sites can say “yes” to more studies without sacrificing their staff, their business, or the integrity of the trial.
Help yourselves: Start generating plain language and ready-to-use documentations, aligned with the protocol, for $145 a month, with Clinials.
