recruitment to clinical trials: adwoa hughes-morley what are the strategies for success?
TRANSCRIPT
Recruitment to Clinical Trials:
Adwoa Hughes-Morley
What are the Strategies for Success?
How easy is it to recruit to clinical trials?
• Across all contexts (McDonald et al, 2006)– 53% of trials are awarded an extension– 45% recruit less than 80% of their target– 31% of trials recruit successfully
• In the pharmaceutical sector (Barnes, 2006)– 80% of all trials fail to meet their recruitment target
• In primary care (Bower et al, 2007) – 29% recruit according to schedule
• We don’t know about the scale of the problem for mental health trials
Consequences of under recruitment
1. Unrepresentative sample = lack of external validity
2. Reduction of statistical power = increased probability of type II error
3. Inhibits the development of reliable evidence and delays adoption of effective interventions.
4. Costly5. Is it ethical?
Barriers to recruitment (Spaar et al, 2009)
SYSTEM RELATED• Lack of study
staff• Multi-centre trials• Inexperienced/
inefficient governance bodies
• Availability of the intervention
INDIVIDUAL• Treatment
preferences of health care providers
• Patient aversion to randomisation
TRIAL-DESIGN-RELATED
• Doubted scientific rationale of trial question
• Doubted relevance of the trial question
• Complexity of the trial
• Restrictive eligibility criteria
Strategies used to improve recruitment to RCTs (Treweek et al, 2010)
1. Open RCT versus blinded RCT2. Placebo versus other comparator3. Other change to trial design versus
conventional RCT design4. Modification to the consent form or
process– Opt-out consent versus opt-in consent– Consent to experimental care versus usual
consent– Consent to standard care versus usual consent– Refusers choose treatment versus usual
consent– Physician modified consent versus usual
consent– Participant modified consent versus usual
consent
5. Financial incentives for participants6. Telephone reminders7. Modification to the training given to
recruiters8. Greater contact between trial
coordinator and trial sites
9. Modification to the approach made to potential participants
– Educational video versus standard information– Educational video with written information versus
written information– Telephone screening versus face-to-face
screening– Enhanced recruitment package versus standard
recruitment package– Enhanced recruitment package with baseline data
collected by telephone versus standard recruitment
– package– Enhanced recruitment package with recruitment
at churches versus standard recruitment package– Clinical trial booklet with standard information
versus standard information– Home safety questionnaire with trial invitation
versus trial invitation– Positive framing of side effects versus neutral
framing– Negative framing of side effects versus neutral
framing– Interactive computer presentation of trial
information versus audio-taped presentation– Writing treatment effect is 'twice as fast' in trial
information versus writing 'half as fast'– Total information disclosure versus standard
disclosure– Electronic completion of screening questionnaire
versus standard paper completion– Oral completion of screening questionnaire
versus standard paper completion
Which recruitment methods have evidence of effectiveness?
1. Telephone reminders to non-responders (Nystuen 2004)
2. Opt-out procedures requiring potential participants to contact the trial team if they do not want to be contacted about a trial (Trevena 2006)]
3. Open label trials rather than blinded (Avenell 2004; Hemminki 2004)
CADET RecruitmentAccumulative Recruitment per Site
0
100
200
300
400
500
600
700Ju
n-09
Aug
-09
Oct
-09
Dec
-09
Feb
-10
Apr
-10
Jun-
10
Aug
-10
Oct
-10
Dec
-10
Month
No
Rec
ruit
ed
Target Per Site
Site A
Site B
Site C
All sites actual
All sites target
ACUDep Trial
43
73
113139
183
580
540
500
460
420
380
220
180
140
100
340
0
640
300
60
20
260
610
577 583
614
551
499
450
356
262
0
2142
730717
696
648
600600
552
504
456
0
100
200
300
400
500
600
700
No
v-0
9
De
c-0
9
Ja
n-1
0
Fe
b-1
0
Ma
r-1
0
Ap
r-1
0
Ma
y-1
0
Ju
n-1
0
Ju
l-1
0
Au
g-1
0
Se
p-1
0
Oc
t-1
0
No
v-1
0
De
c-1
0
Ja
n-1
1
Fe
b-1
1
Ma
r-1
1
Ap
r-1
1
Ma
y-1
1
Month
Nu
mb
er
rec
ruit
ed
Original target (640)
Actual recruitment
Projection for over-recruitment (capped)
Why was recruitment in these trials Successful?
• GP practice database searches• Broad inclusion criteria• Simple study procedures
– (assessments not lasting more than 1.5hours)• Identifying problems early through close
monitoring• Compensating for under-recruitment, by over-
recruiting elsewhere• Telephone follow ups (CADET)• The MHRN and PCRN involvement• Ensuring adequate therapist capacity
Barriers to recruitment in your trials
SYSTEM RELATED INDIVIDUAL TRIAL-DESIGN-RELATED
Adwoa Hughes-Morley
01392 725794Mood Disorders Centre
University of Exeter, Washington Singer Laboratories, Exeter, EX4 4QG.