Table 1.
Percent of trials (N=135) with reported reasons for slow accrual, by phase of trial*
| Categories and Reasons for Slow Accrual | Phase 1 (N=69) | Phase 2 (N=66) |
|---|---|---|
| Safety/Toxicity | 48% | 20% |
| Enrollment slowed/halted due to safety/toxicity but not a DLT | 19% | 6% |
| Dose Limiting Toxicity (DLT) leading to dose reduction | 16% | 2% |
| Condense Adverse Event Protocol Reporting (CAEPR) update required/RRA/Action letter | 9% | 11% |
| FDA holds or amendments | 3% | 0% |
| Safety-other | 1% | 2% |
| Study Design/Protocol | 42% | 33% |
| Longer than expected pre-specified halt/change to enrollment due to interim analyses, stopping rules, data review by DMC | 20% | 12% |
| Safety observation periods/safety run-in taking longer than planned and slowing accrual (but enrollment not stopped) | 10% | 9% |
| Treatment schedule, procedures, or requirements causing undue patient burden leading to slow enrollment | 6% | 5% |
| Design/protocol-other | 6% | 3% |
| Trial complexity | 0% | 5% |
| Eligibility | 41% | 35% |
| Strict eligibility criteria | 23% | 14% |
| High rate of screen failures | 12% | 9% |
| Rare disease | 4% | 11% |
| Eligibility-other | 1% | 2% |
| Institutional/PI/Administrative | 30% | 23% |
| Delays due to staffing/management/operational issues | 14% | 9% |
| Site initiated amendments | 6% | 5% |
| Competing trials within institution | 4% | 3% |
| Low rate of internal referrals | 4% | 2% |
| Institution/admin-other | 1% | 2% |
| Scientific review internally | 0% | 2% |
| IRB/Site Activation | 16% | 29% |
| Extended delays for IRB approval and/or site activation at planned sites | 7% | 15% |
| Planned site(s) have not yet activated trial/were removed | 4% | 12% |
| Trial open at one or a limited number of institutions limiting population access | 4% | 2% |
| CTEP Administrative Issues | 7% | 4% |
| CTEP requests for amendments (not related to safety) | 3% | 2% |
| CTEP-other | 4% | 2% |
| Environment/External Issues | 6% | 8% |
| Newly approved drugs for disease/changes in standard of care | 6% | 6% |
| Environ/external-other | 0% | 2% |
| Drug Supply | 5% | 4% |
| Lack of available drug supply causing accrual delays/discontinued | 4% | 2% |
| Company not willing to supply drug/withdrew support | 1% | 0% |
| Drug-other | 0% | 2% |
| Budget/Insurance Issues | 1% | 11% |
| Loss of study funding | 0% | 5% |
| Study procedures or drug not being covered by insurance/reimbursed | 1% | 3% |
| Low reimbursement rate negatively impacting enrollment | 0% | 3% |
| No Reason Given | 6% | 12% |
*
Sorted in descending order by Phase 1 trial slow accruing reasons