Table 2 Reasons for recruitment failure obtained from interviews and journal publications
Reported reasons | Frequency (from interviews n = 49) a | Frequency (from publications n = 131) g [4] |
|---|---|---|
Funding-related | ||
Initial funding insufficient (including lack of funding for planning; inadequate financial planning) | 10 | 15 |
Additional funding for recruitment escalation/prolongation unavailable | 1 | 6 |
Initial funding withdrawn when slow recruitment became apparent | 0 | 4 |
Research environment-related | ||
Delay in opening recruitment sites (e.g., delayed ethical approval, new regulatory acts) | 8 | 7 |
High bureaucratic burden for clinical researchers (e.g., GCP regulations) | 2 | 3 |
Patients not seeking trials in high-quality health care system with many options (lack of incentive) | 6 | 0 |
Decentralized health care system with many small hospitals and few referrals in Switzerland (e.g., because of restrictive regional insurance contracts; in Germany peripheral hospitals often provide specialized care and refer only severely ill patients to tertiary care hospitals) | 4 | 0 |
General mistrust in research (unbalanced views in media, no public figures as role model to encourage trial participation) | 3 | 4 |
Concurrent competing trials (particularly if other trial in same patient population pays more—see below “Financial conflicts of interest”) | 6 | 11 |
New evidence from other study about effectiveness of trial intervention (e.g., change of standard care during prolonged trial)—affects “equipoise” for recruiters and participants (see below) | 4 | 28 |
Design-related b | ||
Research question insufficiently compelling (e.g., perceived as little relevant for patients and the scientific community) | 5 | 0 |
Low prevalence of condition of interest (seasonal effects, rare diseases) | 7 | 2 |
Too narrow eligibility criteria | 12 | 59 |
Overoptimistic/unreliable recruitment estimates c (e.g., no pilot study; no empirical data; insufficient feasibility checking; weak commitment from centers) | 26 | 10 |
Too few recruiting sites planned or too few study staff (e.g., recruiters, limited engagement of study nurses) | 7 | 0 |
Recruitment insufficiently compatible with routine clinical practice (e.g., urgent transfers from intensive care, different treatment availabilities at different centers or at weekends, referrals too late to tertiary care) d | 7 | 11 |
Lack of methodological/logistical support (e.g., from contract research organization, or clinical trial unit) | 4 | 7 |
Trial design too difficult to explain or implement (e.g., complex interventions, factorial design) | 7 | 4 |
Unclear eligibility criteria or enrolment process (e.g., regarding timing of randomization or responsibilities of involved investigators/personnel) | 0 | 6 |
Ineffective screening/advertising strategy (e.g., email instead of phone call, newspaper campaign only) | 0 | 5 |
Patients approached in inconvenient situation (e.g., women in labor, patients in ICU) | 0 | 5 |
Lack of patient engagement in trial design/planning | 4 | 0 |
Trial team/recruiter-related | ||
Lack of equipoise e | 4 | 34 |
High administrative burden/time constraints/other priorities | 4 | 11 |
Lack of incentive (e.g., financial, academic recognition, career advancement) | 2 | 4 |
Lack of engagement/cooperation (e.g., recruiters (practicing clinicians) unaware of trial, recruiters not involved with study team, departments not referring patients to trial recruiters) | 12 | 4 |
Lack of competence/training/experience (includes inadequate planning; “enthusiasm is not enough,” staff turnover) | 11 | 0 |
“Trial fatigue” (motivation compromised due to recurrent prolongation of recruitment period) | 3 | 0 |
Financial conflict of interest (e.g., trial results favoring conservative treatment over surgery may lead to less earnings; other trial in same patient population pays more—see above “Concurrent competing trials”) | 2 | 1 |
Participant-related | ||
Lack of equipoise f | 6 | 40 |
High burden (e.g., many visits, invasive procedure/biopsies, long questionnaires, costs) | 9 | 20 |
Language or cultural barriers | 1 | 4 |
Lack of financial incentive | 0 | 2 |
Lack of encouragement from patient support organizations | 0 | 1 |
Lack of trust due to short -term relationship with healthcare team (e.g., acute care vs chronic conditions (e.g., dialysis patients)) | 2 | 0 |