recruitment to trials. background recruitment of participants is a very important issue. the general...
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Recruitment to Trials
Background Recruitment of participants is a
VERY important issue.
The general consensus is that most trials under recuit.
Poor Recruitment Poor or slow recruitment to trials leads to
the following problems: Increased risk of Type II error (concluding,
erroneously there is no difference); Delay in implementing research findings; Research commissioners may seek other
INFERIOR but quicker evaluative methods of research.
How common is the problem? There is little quantitative data to
support the qualitative view that many trials under recruit.
One study in USA noted that of 41 trials 34% failed to achieve sample size only another 34% got sample size on time.
Survey To ascertain whether poor trial
recruitment was as poor as believed we undertook a survey of corresponding authors of a sample of trials published in 2000 and 2001.
Puffer & Torgerson 2002;Unpublished
Method We identified all, individually,
randomised trials published in the BMJ and Lancet years 2000 to 2001.
Corresponding authors were emailed a brief questionnaire asking about recruitment problems.
One email reminder was sent.
Results We emailed 196 authors of
individually randomised trials. 33 were bounced back from invalid
email addresses. We received 79 valid responses
(48%).
Recruitment Problems
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Problems Extension Both Funds
Recruitment Multicentred trials had significantly more
problems than single centred studies (51% vs 23%; p = 0.02).
Primary and Secondary trials had similar problems 43% and 39% primary vs secondary.
No significant age difference 48 years vs 52 years for good recruiters vs poor recruiters.
Authors’ comments Facilitate
Secondary care Use previously
successful methods Few exclusion
criteria large sampling frame
Pilot study
Hinder Competing with
other trials. Ethics. Inaccurate
incidence. Clinician
resistance. Narrowly defined
population.
Summary of Comments Recruitment is a problem in the
MAJORITY of trials. Worse in multicentred trials. Need to use pilot studies. Need to use tried and tested
strategies. Need to use large sampling frames.
Examples of poor recruitment York backpain trial needed 300
attained 180. MRC backpain needed 1300
(achieved target but needed extra funds and extended recruitment).
Vein graft trial needed 1200 got 100 (trial collapsed).
SAPPHIRE trial is under-recruiting.
DAMASK recruitmentDamask Overall Recruitment - Oct 2003
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Nov-02 Dec-02 Jan-03 Feb-03 Mar-03 Apr-03 May-03
Jun-03 Jul-03 Aug-03
Sep-03 Oct-03 Nov-03 Dec-03 Jan-04 Feb-04 Mar-04
Target 0 0 0 0 0 42 84 126 168 210 252 294 336 378 420 462 504
Actual 2 4 5 12 24 39 57 85 107 135 165 183
Nov-02 Dec-02 Jan-03 Feb-03 Mar-03 Apr-03May-03
Jun-03 Jul-03Aug-03
Sep-03 Oct-03 Nov-03 Dec-03 Jan-04 Feb-04 Mar-04
Hip protector trial Aimed to recruit 4500 women at risk
of hip fracture to wear hip protectors or act as controls.
Used a combination of GP practices and publicity.
Expected 10% pick up. Pilot showed 2.5%.
Other problems Hip protector trial was a
multicentred study (orginally 5 centres).
Two centres did not start on time, 1 was abandoned, the other started late and only got 50% of expected recruits.
What did we do? Increased eligibility criteria. Mailed out to more GPs Publicity Enrolled a 6th Centre.
Hip Protector TrialHip Protector Trial Recruitment
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Calcium and D recruitment Again we recruited women with 1+ risk
factors for hip fracture over 70 years. Again overestimated recruitment rates at
10%. Pilot showed a recruitment rate of 5%. We doubled the number of GPs to be
included in study.
Other problems Calcium and D trial was a
multicentred study. One centre was late in starting but
eventually DID recruit its target.
Calcium and D trialCalcium and Vitamin D Trial Recruitment
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Recruiting Doctors Often recruting trial participants is
only part of the problem need to recruit doctors as well.
Primary care physicians, unlike secondary care doctors, do not have a career incentive to become involved in research.
GP recruitment Rate We paid both sets of GPs £50 to mail
out prepaid envelopes. For calcium and D we also paid GPs
£30 per patient randomised to active treatment.
Required practice nurse to see patient for 20 minutes.
Which trial recruited most GPs?
GP Recruitment
Participant Recruitment
4898766103
3452 35250
20000400006000080000
Cal
cium
and
Vita
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D
Hip
Pro
tect
ors
Trial
Nu
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f w
om
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aged
70+
Womencontacted
Women agreed toparticipate
MRC RECORD Trial MRC RECORD trial recruited people
from fracture clinics. Under recruited due to over
optimistic recruitment predictions. BUT could not increase number of
centres easily due to budget restraints.
What was done? Payment to trial centres was made
conditional on recruitment rates. Initial contracts for 6 months of a research nurse.
Poor performing centres were closed or finance was reduced.
Trial extension sought and was given.
RECORD result RECORD trial will be late and not
achieved initial sample size. Event rate was higher than expected so loss of power will not occur.
Evidence based recruitment?
Not many RCTs of different methods of recruitment. Cooper et al, showed using a patient preference trial
had not + or – effect on recruitment rates. RCT of nurses vs consultants for prostate cancer trial –
no difference. RCT of trial co-ordinator visits to centres vs mailing
recruitment packs in French cancer trial – no difference. Two open RCTs showed increase in recruitment. Education of GPs shows increase in recruitment Case control data of Zelen’s method does show
increased recruitment rates.
Qualitative methods & recruitment
Donovan and colleagues introduced a ‘rolling’ qualitative research process into patient recruitment for a trial on prostate cancer.
Donovan et al. BMJ 2002;325:766-770
Percent of eligible men recruited
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Authors’ conclusions
“Embedding the controversial ProtecT randomised trial within qualitative research allowed detailed investigation of the presentation of study information by recruiters and its interpretation by participants”
“Changes to the content and delivery of study information increased recruitment rates from 40% to 70%”
Oh Dear As we ALL now know before and after
studies CANNOT infer causality. Interesting data BUT we NEED an RCT to
be sure that this intervention does improve recruitment rates.
There is a natural tendency for recruitment rates to be poor at the start of a study anyway.
‘Natural’ changes in recruitment rates.Hip Protector Trial Recruitment
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DAMASK monthly recruitment
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N D J F M A M J J A S O
NB – no qualitative research intervention.
Recruitment Solutions? Assume from day 1 recruitment
WILL be difficult and delayed. Find solutions from the beginning
(e.g. extra ethics permission, loosening inclusion criteria).
In multicentred trials tailor finance to each centre’s performance.
Summary Recruitment is an important issue. Most trials under-recruit. Careful attention needs to be paid to
recruitment issues from the start.