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Initial funding withdrawn when slow recruitment became apparent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
|