Highlights
- Approximately 31.1% of randomized clinical trials (RCTs) approved by ethics committees are discontinued prematurely, with inadequate participant recruitment serving as the primary cause in 45.4% of those cases.
- A significant transparency gap exists: while 92.3% of industry-sponsored trials made their results publicly available, only 66.3% of non-industry trials did the same.
- Industry-sponsored trials are approximately three times more likely to avoid discontinuation due to recruitment issues compared to academic or investigator-initiated trials (OR 0.32).
- While nonregistration has improved (only 5.8% of trials remained unregistered), the failure to publish results remains a critical source of research waste, particularly in the academic sector.
Background: The Persistent Challenge of Research Waste
The concept of ‘research waste’ was famously quantified by Chalmers and Glasziou, who estimated that up to 85% of investment in biomedical research is wasted due to poor question selection, flawed design, nonpublication, and biased reporting. Among the most critical stages where this waste occurs is the transition from a protocol approved by an ethics committee to a completed, published study. Historically, data from the early 2000s suggested that nearly a third of trials were discontinued, often without the medical community ever learning from the participants’ contributions.
To address these concerns, international standards such as the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement and legal mandates for registry reporting (e.g., ClinicalTrials.gov) were established. However, despite these regulatory advancements, the trajectory of randomized clinical trials (RCTs) remains fraught with obstacles. Understanding the contemporary landscape of trial fate is essential for funders, ethics committees, and investigators to implement more effective oversight and support mechanisms.
The ASPIRE Study Design: A Comprehensive Audit of Trial Fate
The Adherence to SPIRIT Recommendations (ASPIRE) study conducted a systematic review to assess the current status of RCT transparency and completion. The researchers analyzed 347 RCT protocols that received approval from research ethics committees in 2016 across four nations: the United Kingdom, Switzerland, Germany, and Canada. This multi-national approach provided a robust cross-section of the regulatory environments in Western clinical research.
The study specifically focused on trials that intended to assign participants to interventions to study health outcomes. To ensure a focus on definitive clinical research, the reviewers excluded pilot studies, feasibility trials, phase 1 trials, and trials that never actually commenced. In July 2024, the research team performed an exhaustive search for trial registrations and results in public registries and peer-reviewed journals. In cases where the status remained ambiguous, the investigators contacted principal investigators or ethics committees directly to ensure the highest possible data accuracy.
Key Findings: Nonregistration, Discontinuation, and the Publication Gap
The results of the ASPIRE systematic review provide a sobering look at the efficiency of the clinical research enterprise. While some progress has been made in trial registration, the hurdles of recruitment and publication remain formidable.
Improving Registration, Stagnant Completion
Of the 347 included trials, only 20 (5.8%) remained unregistered. This represents a significant improvement over historical cohorts, suggesting that the culture of registration is becoming more deeply embedded in the clinical research workflow. However, the completion rate tells a different story. Nearly one-third of the trials (31.1%) were discontinued prematurely. When the researchers investigated the causes for these stoppages, poor recruitment emerged as the dominant factor, accounting for nearly half (45.4%) of all discontinuations.
The Industry vs. Academic Divide
One of the most striking findings of the study was the disparity between industry-sponsored trials and non-industry-sponsored (academic or investigator-initiated) trials. Results from industry-sponsored trials were significantly more likely to be available to the public than those from non-industry sources (92.3% vs. 66.3%).
This gap appears to be driven by two primary factors. First, industry sponsors demonstrated a much higher rate of reporting results directly within trial registries. 84.5% of industry trials reported registry results, compared to a meager 10.2% of non-industry trials. Second, industry-sponsored trials were more resilient to recruitment failures. Multivariable logistic regression indicated that industry-sponsored trials were significantly less likely to be discontinued due to poor recruitment (adjusted odds ratio, 0.32; 95% CI, 0.15-0.71).
Public Availability of Results
Overall, 79.5% of the trials made their results publicly available in some form. While this is a majority, it implies that one in five trials—involving thousands of human participants—yielded no public data. The discrepancy in registry reporting is particularly noteworthy; many academic researchers still view peer-reviewed publication as the only valid form of dissemination, whereas industry sponsors are more attuned to (and often legally bound by) registry reporting requirements such as those mandated by the FDA or EMA.
Expert Commentary: Analyzing the Disparities
The findings of the ASPIRE study highlight a structural vulnerability in academic clinical research. While industry sponsors often have dedicated clinical operations teams, robust budgets for recruitment marketing, and professional regulatory affairs departments, academic investigators frequently rely on overstretched clinical staff and limited grant funding. The fact that industry trials are three times more likely to survive recruitment challenges suggests that the ‘professionalization’ of trial management is a major determinant of success.
Furthermore, the failure of non-industry trials to utilize registries for results reporting is a missed opportunity for transparency. Registry reporting is often faster than the traditional peer-review process and ensures that even negative or ‘uninteresting’ results are accessible to the scientific community, thereby preventing other researchers from repeating unsuccessful interventions.
The study also raises ethical questions. When a trial is discontinued due to poor recruitment or when results are not published, the altruistic contribution of the participants is largely squandered. Ethics committees, which are responsible for protecting these participants, must evolve from ‘gatekeepers’ who only approve protocols to ‘overseers’ who monitor the trial’s progress and ensure its ultimate dissemination.
Conclusion: Moving Toward Accountability
The ASPIRE systematic review serves as a call to action for the global research community. To mitigate the ongoing challenge of research waste, the authors suggest that requirements enforced by funders and ethics committees must be strengthened. Potential interventions include:
- Mandating registry reporting as a condition for future funding.
- Providing academic researchers with better institutional support for recruitment and trial management.
- Empowering ethics committees to require annual updates on trial status and results dissemination.
- Evaluating the impact of legal obligations for results reporting across different jurisdictions.
If the medical community is to uphold its social contract with trial participants, the gap between protocol approval and results publication must be closed, particularly within the academic sector.
References
Speich B, Taji Heravi A, Schönenberger CM, et al. Nonregistration, Discontinuation, and Nonpublication of Randomized Trials: A Systematic Review. JAMA Netw Open. 2025;8(9):e2524440. doi:10.1001/jamanetworkopen.2025.24440
Chalmers I, Glasziou P. Avoidable waste in the production and reporting of research evidence. Lancet. 2009;374(9683):86-89.
