Four Critical Questions to Ask Before Signing with a ‘Big Five’ CRO

Is a Big Five CRO the Right Fit—or Just the Familiar Choice?

For biotech and mid-sized pharma companies, selecting the right CRO partner can make the difference between a successful, on-time clinical development program and one plagued by delays, budget overruns, and management headaches. 

While large, global CROs offer undeniable infrastructure and scale advantages, many sponsors report experiencing diminishing returns on their CRO investments—including canned strategies, inflexible approaches, costly protocol changes and lack of team continuity on their study. Frustrations with the operations of the five biggest CROS have led to a phenomenon known as Big Five Fatigue.

Before committing your next study to a large CRO, consider asking these four critical questions: 

Question 1: "How often will I work with specialists in my specific indication—not just therapeutic area?" 

The distinction between therapeutic area experience and specific indication expertise is crucial, especially in complex fields like oncology and rare disease. Large CROs may showcase impressive therapeutic breadth, but depth in your particular indication can make a meaningful difference in study execution. 

• What to listen for: Vague references to general therapeutic expertise rather than specific experience with your indication or mechanism of action. Request concrete examples of similar studies and outcomes in your exact indication. 

Specialized knowledge in your specific indication directly impacts protocol design, site selection, patient recruitment strategies, and overall study efficiency. At Precision for Medicine, over 70% of our trials are in oncology, creating a depth of specialized experience that translates to operational advantages. 

Question 2: "What's your team's annual turnover rate, and how do you ensure continuity on my study?" 

Staff turnover represents one of the most disruptive elements in clinical research partnerships. The industry average CRO turnover rate hovers around 20%, but this figure varies significantly between organizations. 

• What to listen for: Listen for specific turnover metrics, not just assurances of "low turnover" or "great retention." Ask about specific continuity planning and knowledge transfer protocols. 

Each staff transition creates knowledge gaps, relationship disruptions, and operational delays that compound over time. With less than half the average turnover, Precision for Medicine provides significant team stability and continuity. 

Question 3: "How flexible are you with mid-study changes and protocol amendments?" 

Protocol amendments are virtually inevitable as new data emerges. The ability to adapt quickly can preserve months of development time. 

• What to listen for: Multiple approval layers often signal longer implementation times. Try to understand their standard timelines for implementing common types of amendments, and the approval processes these changes must navigate.  

Protocol amendment implementation timelines can vary dramatically between CROs. Specialized providers with streamlined processes can often implement changes in a fraction of the time required by large organizations with more complex approval hierarchies. 

Question 4: "What resources will I need to dedicate to managing our relationship?" 

The "true cost" of a CRO relationship extends well beyond the contract value to include the internal resources required for oversight, coordination, and governance. 

• What to listen for: Realistic assessments of sponsor resource requirements, communication expectations, and escalation pathways. Be wary of assurances that minimal oversight will be required. 

Sponsors frequently report spending more internal resources managing CRO relationships than initially projected. Understanding these requirements upfront allows for more accurate financial and resource planning. 

When Scale Slows You Down, a Right-Sized CRO Keeps You Moving

Specialized providers have a demonstrated ability to deliver comparable quality with greater efficiency for specific therapeutic areas. Organizations like Precision for Medicine have developed purpose-built approaches for oncology and rare disease trials that address many of the challenges sponsors face with larger, more generalized CROs. 

Before defaulting to a large CRO, consider whether a more specialized partner might better align with your specific program needs, timeline objectives, and resource constraints. 

Include Precision in your CRO consideration set. Together we can deliver life-changing therapies without a lifetime of development.