CLINICAL DEVELOPMENT IN ONCOLOGY


the recruitment period for oncology trials lasted over 7 months longer on average compared to non-oncology, and oncology trials had a significantly higher prevalence and frequency of protocol amendments. Among oncology trials with amendments, the average screen failure rate was significantly higher compared to oncology trials without amendments. Notably, screen failure rate was higher for non-oncology compared to oncology on average, though these differences were only significant among Phase I trials. Higher screen failure rates in oncology protocols with amendments indicate that these protocols may have had more selective eligibility criteria compared to oncology protocols without amendments, leading to increased barriers to meeting recruitment goals and a higher chance of termination due to lack of accrual (Parekh, 2022).


The issue of recruitment Although Fogel (2018) hypothesized that recruitment difficulties due to narrow eligibility criteria would be a common cause of amendments among oncology trials, Tufts CSDD found no significant differences when comparing amendments implemented in oncology to non-oncology clinical trials. In fact, non-oncology amendments were slightly more likely to be caused by recruitment difficulties. The definition for an amendment caused by recruitment difficulty in this study included broadening eligibility (inclusion and exclusion) criteria. More specific changes to the protocol due to an amendment were also collected, including any changes to the population description (inclusion/exclusion criteria), regardless of the rationale. Changes to eligibility criteria were most commonly classified under Change in Study Strategy, Regulatory Agency Request, New Data Available, New Safety Data Available, or Other. While no significant differences were observed between changes to the population description in oncology compared to non-oncology amendments, oncology amendments were 6% more likely than non-oncology amendments to note this change, with 61% of all amendments involving changes to the population description. The fact that only 8% of oncology amendments with changes to the population description were classified as being caused by


Dropout rates in oncology were 35% higher than in non-oncology clinical trials


recruitment difficulty suggests that most of these changes were either not specified as broadening the criteria, or that the change was due to some other factor. Further, both oncology and non-oncology had an average increase in the number of inclusion and exclusion criteria between protocol approval and the end of the study. While this does not necessarily mean that eligibility criteria became more or less stringent, it does imply that inclusion and exclusion criteria were not removed. Additionally, oncology amendments were significantly more likely than non-oncology amendments to have a change in medication permitted before or during the trial, which may have similarly broadened or narrowed the eligible target population, depending on the specific change. While the more detailed individual changes to an amendment showed no significant differences in frequency of changes to the population description (inclusion/exclusion criteria) between oncology and non-oncology clinical trials, the former were significantly more likely to include changes to the sample size and twice as likely to have an amendment where the sample size was changed after the end of the recruitment period. Our study finding that oncology amendments were more likely to result in a change in sample size is consistent with academic studies of oncology clinical research indicating that decreasing the sample size, and therefore the power of the study, has become a more common solution to an inability to meet recruitment goals (Olivier, 2024). While recognizing that smaller sample sizes can be necessary to decrease complexity and increase feasibility, the practice of decreasing the sample size during the trial – particularly when implemented during or after the recruitment period – is concerning.


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