A clinical trial protocol is more than a technical document-it’s the blueprint of your study. It guides every aspect of trial conduct, from eligibility and procedures to endpoints and data analysis. Yet, even experienced teams can stumble during protocol development, leading to delays, protocol amendments, and unnecessary costs.
At Lex Clinical, we’ve reviewed and helped optimize dozens of protocols. Our experience shows that most design issues are preventable with the right expertise and foresight. Below, we highlight common pitfalls and how to avoid them.
Pitfall 1: Vague or Unjustified Objectives and Endpoints
Problem: Objectives that are too broad or poorly defined often result in vague endpoints, complicating data collection and analysis.
Fix: Start with a clear scientific question and build specific, measurable, and clinically meaningful endpoints. Align them with regulatory and payer expectations from the beginning.
Pitfall 2: Overly Complex Inclusion/Exclusion Criteria
Problem: Narrow criteria may limit recruitment or make the study population unrepresentative of real-world patients.
Fix: Balance internal validity with external generalizability. Use real-world data or expert input to assess feasibility and recruitability early.
Pitfall 3: Inadequate Feasibility Assessment
Problem: Protocols may look good on paper but fail in real settings due to underestimated burdens on patients or sites.
Fix: Conduct operational feasibility assessments before finalizing the protocol. Include feedback from investigators, coordinators, and even patients.
Pitfall 4: Lack of Patient-Centered Design
Problem: Protocols often neglect patient perspectives, leading to dropouts or protocol deviations.
Fix: Apply patient engagement strategies during protocol development. Tools like patient advisory boards or mock trial visits can reveal usability issues.
Pitfall 5: Misaligned Study Design with Regulatory Pathways
Problem: Choosing the wrong design (e.g. underpowered, wrong comparator, or inappropriate endpoints) can hinder regulatory approval.
Fix: Seek early scientific or regulatory advice from agencies like EMA or FDA. Involve statisticians and regulatory experts at the planning stage.
Pitfall 6: Weak Data Quality Plans
Problem: Vague data handling or monitoring plans can lead to inconsistent data and audit findings.
Fix: Integrate a data integrity and monitoring strategy within your protocol. Align with GCP and define quality metrics from the start.
How Lex Clinical Helps You Get It Right
We partner with sponsors and CROs to co-create protocols that are scientifically sound, operationally feasible, and regulatory-compliant. Our support includes:
✅ Protocol review and risk assessment
✅ Early input on study design, comparators, and endpoints
✅ Feasibility testing with real-world input
✅ Integration of patient and clinician feedback
✅ Alignment with GCP, EMA, MDR, and HTA expectations
A well-designed protocol doesn’t just pass review-it accelerates approvals, reduces amendments, and increases trial success.
Keywords
clinical trial protocol, protocol design, GCP compliance, patient-centered trials, feasibility studies, protocol amendments, EMA scientific advice, MDR, clinical trial success, Lex Clinical, regulatory strategy, endpoint selection, real-world feasibility
References
- Getz KA, Campo RA. Variability in protocol design complexity by phase and therapeutic area. Drug Inf J. 2012;46(1):63-70. doi:10.1177/0092861511431883
- U.S. FDA. Guidance for Industry: Oversight of Clinical Investigations-A Risk-Based Approach to Monitoring
- EMA. Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials
- Ennis L, Wykes T. Impact of patient involvement in mental health research: longitudinal study. Br J Psychiatry. 2013;203(5):381-386. doi:10.1192/bjp.bp.112.119818
- Heiat A, Gross CP, Krumholz HM. Representation of the elderly, women, and minorities in heart failure clinical trials. Arch Intern Med. 2002;162(15):1682-1688. doi:10.1001/archinte.162.15.1682
Ready to Optimize Your Next Protocol?
A solid clinical trial protocol can save time, reduce amendments, and build trust with regulators and sites alike. At Lex Clinical, we offer tailored consultancy to help you design protocols that are scientifically robust, patient-friendly, and operationally feasible.
Let’s collaborate to set your trial up for success.
Contact us to schedule a protocol review or design consultation.