Planning your clinical trial: Avoidable mistakes

Clinical trials are not cheap to conduct, and with data integrity and patient safety being so critical, it is essential to get everything right. The key to success can be found in study planning, which has long been recognised as a major determinant of trial validity, efficiency, and regulatory acceptability [1].

It might be surprising to learn that there are several common traps that Sponsors and Contract Research Organisations (CROs) frequently fall into when planning clinical trials. Analyses of failed or delayed trials consistently identify weaknesses in design, feasibility assessment, and operational planning as common root causes [2,3]. We list a few of the more obvious oversights here to help ensure trial success and generation of a reliable and meaningful data set.

Poor Study Design: Failing to take appropriate care when designing a study can lead to confounding observations or inability to meet objectives. Inadequate sample size justification, inappropriate randomisation, and failure to consider the necessity or structure of control groups are well-documented contributors to biased or uninterpretable results [4,5].

Ill-defined Endpoints: Failing to clearly define primary and secondary endpoints undermines a trial’s ability to meet its desired outcomes. Endpoints must be prespecified, clinically relevant, and statistically appropriate. Poor endpoint selection and vague definitions have been associated with regulatory uncertainty and inconclusive findings [6,7,8]. Inclusion and exclusion criteria similarly require careful consideration, as overly restrictive or poorly justified criteria can impair recruitment and limit generalisability [9].

Recruitment and Retention of Participants: Sponsors often underestimate recruitment and retention challenges, particularly in early-phase studies. Evidence shows that complex procedures, high visit burden, and participant discomfort reduce enrolment and increase attrition [10,11,12]. Failure to recruit or retain sufficient participants can compromise statistical power or increase costs and timelines if replacement is required.

Protocol Adherence: Protocol deviations can introduce bias and threaten data integrity. Excessive protocol complexity and poor operational feasibility have been repeatedly linked to increased deviation rates and site burden [13,14]. Ensuring that procedures are deliverable by site staff throughout the study is essential to maintaining data quality.

Statistical Planning: Insufficient consideration of statistical methods during protocol development can lead to confounded data or failure to meet planned objectives. Early and continuous involvement of statisticians in outcome selection, randomisation, and sample size determination is critical [15].

The role of the statistician extends throughout the study lifecycle, including oversight of randomisation, contribution to data interpretation, and assurance of analytical integrity.

Ethical and Regulatory Compliance: Failure to address ethical or regulatory requirements early can delay approvals or result in study suspension or termination. Embedding Good Clinical Practice (GCP) and regulatory expectations into protocol design from the outset is essential for timely approval and conduct [15,16].

Monitoring and Quality Control: Appropriate monitoring strategies and quality management systems are fundamental to ensuring data integrity and participant safety. Traditional and emerging risk-based monitoring approaches were already recognised prior to 2015 as important tools for effective oversight [17].

Site Selection: Not all clinical research units are equivalent in terms of infrastructure, experience, and quality systems. Poor site selection has been shown to contribute to recruitment delays, protocol deviations, and compromised data quality [18].

Budget and Resource Planning: Underestimating financial or personnel requirements can result in delays, compromised data quality, or premature study termination. Accurate forecasting and realistic budgeting have long been recognised as essential elements of trial feasibility [19,20].

Open Communication: Clear communication between sponsors, investigators, and study teams is essential for successful trial conduct. Poor communication has been associated with misunderstandings, operational errors, and delays [21].

Addressing these common pitfalls during the planning phase increases the likelihood of conducting a scientifically sound and efficient clinical trial. As described in our Insider's Insight, early-stage tools such as concept or synoptic protocols can support alignment and risk identification across multidisciplinary teams [22].

References

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15. International Council for Harmonisation (ICH).ICH E9: Statistical principles for clinical trials. 1998.
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17. Morrison BW, et al. Monitoring the quality of conduct of clinical trials: a survey of current practices. Clin Trials. 2011 Jun;8(3):342-9.
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20. Wong HH, et al (2014). EXAMINATION OF CLINICAL TRIAL COSTS AND BARRIERS FOR DRUG DEVELOPMENT. ASPE Report. [accessed Feb 2015]
21. Manias E, et al. Communication failures during clinical handovers lead to a poor patient outcome: Lessons from a case report. SAGE Open Med Case Rep. 2015 Apr 29;3:2050313X15584859.
22. Niche Science & Technology Ltd. An Insider’s Insight to Concept Protocols. 2014 [accessed Feb 2015].