Experience with a hybrid recruitment approach of patient-facing web portal screening and subsequent phone and medical record review for a neurosurgical intervention trial for chronic ischemic stroke disability (PISCES III)
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Abstract
Background
Recruitment of participants is the greatest risk to completion of most clinical trials,
with 20–40% of trials failing to reach the targeted enrollment. This is particularly
true of trials of central nervous system (CNS) therapies such as intervention for
chronic stroke. The PISCES III trial was an invasive trial of stereotactically guided
intracerebral injection of CTX0E03, a fetal derived neural stem cell line, in patients
with chronic disability due to ischemic stroke. We report on the experience using
a novel hybrid recruitment approach of a patient-facing portal to self-identify and
perform an initial screen for general trial eligibility (tier 1), followed by phone
screening and medical records review (tier 2) prior to a final in-person visit to
confirm eligibility and consent.
Methods
Two tiers of screening were established: an initial screen of general eligibility
using a patient-facing web portal (tier 1), followed by a more detailed screen that
included phone survey and medical record review (tier 2). If potential participants
passed the tier 2 screen, they were referred directly to visit 1 at a study site,
where final in-person screening and consent were performed. Rates of screening were
tracked during the period of trial recruitment and sources of referrals were noted.
Results
The approach to screening and recruitment resulted in 6125 tier 1 screens, leading
to 1121 referrals to tier 2. The tier 2 screening resulted in 224 medical record requests
and identification of 86 qualifying participants for referral to sites. The study
attained a viable recruitment rate of 6 enrolled per month prior to being disrupted
by COVID 19.
Conclusions
A tiered approach to eligibility screening using a hybrid of web-based portals to
self-identify and screen for general eligibility followed by a more detailed phone
and medical record review allowed the study to use fewer sites and reduce cost. Despite
the difficult and narrow population of patients suffering moderate chronic disability
from stroke, this strategy produced a viable recruitment rate for this invasive study
of intracranially injected neural stem cells.
Trial registration
ClinicalTrials.gov Identifier: NCT03629275
Supplementary Information
The online version contains supplementary material available at 10.1186/s13063-024-07988-z.
Recruiting participants to trials can be extremely difficult. Identifying strategies that improve trial recruitment would benefit both trialists and health research. To quantify the effects of strategies for improving recruitment of participants to randomised trials. A secondary objective is to assess the evidence for the effect of the research setting (e.g. primary care versus secondary care) on recruitment. We searched the Cochrane Methodology Review Group Specialised Register (CMR) in the Cochrane Library (July 2012, searched 11 February 2015); MEDLINE and MEDLINE In Process (OVID) (1946 to 10 February 2015); Embase (OVID) (1996 to 2015 Week 06); Science Citation Index & Social Science Citation Index (ISI) (2009 to 11 February 2015) and ERIC (EBSCO) (2009 to 11 February 2015). Randomised and quasi‐randomised trials of methods to increase recruitment to randomised trials. This includes non‐healthcare studies and studies recruiting to hypothetical trials. We excluded studies aiming to increase response rates to questionnaires or trial retention and those evaluating incentives and disincentives for clinicians to recruit participants. We extracted data on: the method evaluated; country in which the study was carried out; nature of the population; nature of the study setting; nature of the study to be recruited into; randomisation or quasi‐randomisation method; and numbers and proportions in each intervention group. We used a risk difference to estimate the absolute improvement and the 95% confidence interval (CI) to describe the effect in individual trials. We assessed heterogeneity between trial results. We used GRADE to judge the certainty we had in the evidence coming from each comparison. We identified 68 eligible trials (24 new to this update) with more than 74,000 participants. There were 63 studies involving interventions aimed directly at trial participants, while five evaluated interventions aimed at people recruiting participants. All studies were in health care. We found 72 comparisons, but just three are supported by high‐certainty evidence according to GRADE. 1. Open trials rather than blinded, placebo trials . The absolute improvement was 10% (95% CI 7% to 13%). 2. Telephone reminders to people who do not respond to a postal invitation . The absolute improvement was 6% (95% CI 3% to 9%). This result applies to trials that have low underlying recruitment. We are less certain for trials that start out with moderately good recruitment (i.e. over 10%). 3. Using a particular, bespoke, user‐testing approach to develop participant information leaflets . This method involved spending a lot of time working with the target population for recruitment to decide on the content, format and appearance of the participant information leaflet. This made little or no difference to recruitment: absolute improvement was 1% (95% CI −1% to 3%). We had moderate‐certainty evidence for eight other comparisons; our confidence was reduced for most of these because the results came from a single study. Three of the methods were changes to trial management, three were changes to how potential participants received information, one was aimed at recruiters, and the last was a test of financial incentives. All of these comparisons would benefit from other researchers replicating the evaluation. There were no evaluations in paediatric trials. We had much less confidence in the other 61 comparisons because the studies had design flaws, were single studies, had very uncertain results or were hypothetical (mock) trials rather than real ones. The literature on interventions to improve recruitment to trials has plenty of variety but little depth. Only 3 of 72 comparisons are supported by high‐certainty evidence according to GRADE: having an open trial and using telephone reminders to non‐responders to postal interventions both increase recruitment; a specialised way of developing participant information leaflets had little or no effect. The methodology research community should improve the evidence base by replicating evaluations of existing strategies, rather than developing and testing new ones. What improves trial recruitment? Key messages We had high‐certainty evidence for three methods to improve recruitment, two of which are effective: 1. Telling people what they are receiving in the trial rather than not telling them improves recruitment. 2. Phoning people who do not respond to a postal invitation is also effective (although we are not certain this works as well in all trials). 3. Using a tailored, user‐testing approach to develop participant information leaflets makes little or no difference to recruitment. Of the 72 strategies tested, only 7 involved more than one study. We need more studies to understand whether they work or not. Our question We reviewed the evidence about the effect of things trial teams do to try and improve recruitment to their trials. We found 68 studies involving more than 74,000 people. Background Finding participants for trials can be difficult, and trial teams try many things to improve recruitment. It is important to know whether these actually work. Our review looked for studies that examined this question using chance to allocate people to different recruitment strategies because this is the fairest way of seeing if one approach is better than another. Key results We found 68 studies including 72 comparisons. We have high certainty in what we found for only three of these. 1. Telling people what they are receiving in the trial rather than not telling them improves recruitment. Our best estimate is that if 100 people were told what they were receiving in a randomised trial, and 100 people were not, 10 more would take part n the group who knew. There is some uncertainty though: it could be as few as 7 more per hundred, or as many as 13 more. 2. Phoning people who do not respond to a postal invitation to take part is also effective. Our best estimate is that if investigators called 100 people who did not respond to a postal invitation, and did not call 100 others, 6 more would take part in the trial among the group who received a call. However, this number could be as few as 3 more per hundred, or as many as 9 more. 3. Using a tailored, user‐testing approach to develop participant information leaflets did not make much difference. The researchers who tested this method spent a lot of time working with people like those to be recruited to decide what should be in the participant information leaflet and what it should look like. Our best estimate is that if 100 people got the new leaflet, 1 more would take part in the trial compared to 100 who got the old leaflet. However, there is some uncertainty, and it could be 1 fewer (i.e. worse than the old leaflet) per hundred, or as many as 3 more. We had moderate certainty in what we found for eight other comparisons; our confidence was reduced for most of these because the method had been tested in only one study. We had much less confidence in the other 61 comparisons because the studies had design flaws, were the only studies to look at a particular method, had a very uncertain result or were mock trials rather than real ones. Study characteristics The 68 included studies covered a very wide range of disease areas, including antenatal care, cancer, home safety, hypertension, podiatry, smoking cessation and surgery. Primary, secondary and community care were included. The size of the studies ranged from 15 to 14,467 participants. Studies came from 12 countries; there was also one multinational study involving 19 countries. The USA and UK dominated with 25 and 22 studies, respectively. The next largest contribution came from Australia with eight studies. The small print Our search updated our 2010 review and is current to February 2015. We also identified six studies published after 2015 outside the search. The review includes 24 mock trials where the researchers asked people about whether they would take part in an imaginary trial. We have not presented or discussed their results because it is hard to see how the findings relate to real trial decisions.
Background Poor recruitment to randomised controlled trials (RCTs) is a widespread and important problem. With poor recruitment being such an important issue with respect to the conduct of randomised trials, a systematic review of controlled trials on recruitment methods was undertaken in order to identify strategies that are effective. Methods We searched the register of trials in Cochrane library from 1996 to end of 2004. We also searched Web of Science for 2004. Additional trials were identified from personal knowledge. Included studies had to use random allocation and participants had to be allocated to different methods of recruitment to a 'real' randomised trial. Trials that randomised participants to 'mock' trials and trials of recruitment to non-randomised studies (e.g., case control studies) were excluded. Information on the study design, intervention and control, and number of patients recruited was extracted by the 2 authors. Results We identified 14 papers describing 20 different interventions. Effective interventions included: telephone reminders; questionnaire inclusion; monetary incentives; using an 'open' rather than placebo design; and making trial materials culturally sensitive. Conclusion Few trials have been undertaken to test interventions to improve trial recruitment. There is an urgent need for more RCTs of recruitment strategies.
[1
]GRID grid.26009.3d, ISNI 0000 0004 1936 7961, Duke Clinical Research Institute, , Duke University School of Medicine, ; Durham, NC USA
[2
]GRID grid.26009.3d, ISNI 0000 0004 1936 7961, Department of Neurology, , Duke University School of Medicine, ; Duke Box 2900 Bryan Research Building, 311 Research Drive, Durham, NC 27710 USA
[3
]GRID grid.8756.c, ISNI 0000 0001 2193 314X, School of Psychology & Neuroscience, , University of Glasgow, Queen Elizabeth University Hospital, ; Glasgow, Scotland UK
[4
]GRID grid.267308.8, ISNI 0000 0000 9206 2401, Institute for Stroke and Cerebrovascular Disease, , University of Texas Health Science Center, ; Houston, TX USA
[5
]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Department of Neurology, Perelman School of Medicine, , University of Pennsylvania, ; Philadelphia, PA USA
[6
]Department of Neuroscience and Experimental Therapeutics, Albany Medical College,
(
https://ror.org/0307crw42)
Albany, NY USA
[7
]GRID grid.410427.4, ISNI 0000 0001 2284 9329, Department of Neurosurgery, , Medical College of Georgia, ; Augusta, GA USA
[8
]GRID grid.438364.e, ReNeuron Limited., ; Pencoed, Bridgend, UK
[9
]GRID grid.468222.8, The Vivian L. Smith Department of Neurosurgery, , The University of Texas Health Science Center, ; Houston, TX USA
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