The authors have declared that no competing interests exist.
Patrina Caldwell and colleagues performed a systematic review of randomized studies that compared methods of recruiting individual study participants into trials, and found that strategies that focus on increasing potential participants' awareness of the specific health problem, and that engaged them, appeared to increase recruitment.
Recruitment of participants into randomised controlled trials (RCTs) is critical for successful trial conduct. Although there have been two previous systematic reviews on related topics, the results (which identified specific interventions) were inconclusive and not generalizable. The aim of our study was to evaluate the relative effectiveness of recruitment strategies for participation in RCTs.
A systematic review, using the PRISMA guideline for reporting of systematic reviews, that compared methods of recruiting individual study participants into an actual or mock RCT were included. We searched MEDLINE, Embase, The Cochrane Library, and reference lists of relevant studies. From over 16,000 titles or abstracts reviewed, 396 papers were retrieved and 37 studies were included, in which 18,812 of at least 59,354 people approached agreed to participate in a clinical RCT. Recruitment strategies were broadly divided into four groups: novel trial designs (eight studies), recruiter differences (eight studies), incentives (two studies), and provision of trial information (19 studies). Strategies that increased people's awareness of the health problem being studied (e.g., an interactive computer program [relative risk (RR) 1.48, 95% confidence interval (CI) 1.00–2.18], attendance at an education session [RR 1.14, 95% CI 1.01–1.28], addition of a health questionnaire [RR 1.37, 95% CI 1.14–1.66]), or a video about the health condition (RR 1.75, 95% CI 1.11–2.74), and also monetary incentives (RR1.39, 95% CI 1.13–1.64 to RR 1.53, 95% CI 1.28–1.84) improved recruitment. Increasing patients' understanding of the trial process, recruiter differences, and various methods of randomisation and consent design did not show a difference in recruitment. Consent rates were also higher for nonblinded trial design, but differential loss to follow up between groups may jeopardise the study findings. The study's main limitation was the necessity of modifying the search strategy with subsequent search updates because of changes in MEDLINE definitions. The abstracts of previous versions of this systematic review were published in 2002 and 2007.
Recruitment strategies that focus on increasing potential participants' awareness of the health problem being studied, its potential impact on their health, and their engagement in the learning process appeared to increase recruitment to clinical studies. Further trials of recruitment strategies that target engaging participants to increase their awareness of the health problems being studied and the potential impact on their health may confirm this hypothesis.
Before any health care intervention—a treatment for a disease or a measure such as vaccination that is designed to prevent an illness—is adopted by the medical community, it undergoes exhaustive laboratory-based and clinical research. In the laboratory, scientists investigate the causes of diseases, identify potential new treatments or preventive methods, and test these interventions in animals. New interventions that look hopeful are then investigated in clinical trials—studies that test these interventions in people by following a strict trial protocol or action plan. Phase I trials test interventions in a few healthy volunteers or patients to evaluate their safety and to identify possible side effects. In phase II trials, a larger group of patients receives an intervention to evaluate its safety further and to get an initial idea of its effectiveness. In phase III trials, very large groups of patients (sometimes in excess of a thousand people) are randomly assigned to receive the new intervention or an established intervention or placebo (dummy intervention). These “randomized controlled trials” or “RCTs” provide the most reliable information about the effectiveness and safety of health care interventions.
Patients who participate in clinical trials must fulfill the inclusion criteria laid down in the trial protocol and must be given information about the trial, its risks, and potential benefits before agreeing to participate (informed consent). Unfortunately, many RCTs struggle to enroll the number of patients specified in their trial protocol, which can reduce a trial's ability to measure the effect of a new intervention. Inadequate recruitment can also increase costs and, in the worst cases, prevent trial completion. Several strategies have been developed to improve recruitment but it is not clear which strategy works best. In this study, the researchers undertake a systematic review (a study that uses predefined criteria to identify all the research on a given topic) of “recruitment trials”—studies that have randomly divided potential RCT participants into groups, applied different strategies for recruitment to each group, and compared recruitment rates in the groups.
The researchers identified 37 randomized trials of recruitment strategies into real and mock RCTs (where no actual trial occurred). In all, 18,812 people agreed to participate in an RCT in these recruitment trials out of at least 59,354 people approached. Some of these trials investigated novel strategies for recruitment, such as changes in how patients are randomized. Others looked at the effect of recruiter differences (for example, increased contact between the health care professionals doing the recruiting and the trial investigators), the effect of offering monetary incentives to participants, and the effect of giving more information about the trial to potential participants. Recruitment strategies that improved people's awareness of the health problem being studied—provision of an interactive computer program or a video about the health condition, attendance at an educational session, or inclusion of a health questionnaire in the recruitment process—improved recruitment rates, as did monetary incentives. Increasing patients' understanding about the trial process itself, recruiter differences, and alterations in consent design and randomization generally had no effect on recruitment rates although consent rates were higher when patients knew the treatment to which they had been randomly allocated before consenting. However, differential losses among the patients in different treatment groups in such nonblinded trials may jeopardize study findings.
These findings suggest that trial recruitment strategies that focus on increasing the awareness of potential participants of the health problem being studied and its possible effects on their health, and that engage potential participants in the trial process are likely to increase recruitment to RCTs. The accuracy of these findings depends on whether the researchers identified all the published research on recruitment strategies and on whether other research on recruitment strategies has been undertaken and not published that could alter these findings. Furthermore, because about half of the recruitment trials identified by the researchers were undertaken in the US, the successful strategies identified here might not be generalizable to other countries. Nevertheless, these recruitment strategies should now be investigated further to ensure that the future evaluation of new health care interventions is not hampered by poor recruitment into RCTs.
Please access these Web sites via the online version of this summary at
The
The US National Institutes of Health provides information about
The UK National Health Service Choices Web site has information for patients about
The UK Medical Research Council Clinical Trials Units also provides information for patients about
MedlinePlus has links to further resources on
The Australian Government's National Health and Medical Research Council has information about
The randomised controlled trial (RCT) provides the most reliable evidence for evaluating the effects of health care interventions
Historically recruitment of participants for RCTs has been by “trial and error”
The aim of this study was to identify effective recruitment strategies for clinical RCTs by systematically reviewing randomised studies that compare consent rates, or other methods of measuring consent for two or more recruitment methods used, to approach potential RCT participants for trial participation (these studies are termed recruitment trials).
A protocol for this systematic review had not been registered before the review commenced, although the abstracts of previous versions of this systematic review were published in 2002 (International Clinical Trials Symposium: improving health care in the new millennium)
All randomised and quasi-randomised studies that compared two or more methods of recruiting study participants to a real phase III RCT or mock RCT (where no actual trial occurred) were included. Studies that assessed recruitment to observational studies, questionnaires, health promotional activities, and other health care interventions and nonrandomised studies of recruitment strategies were excluded. Where more than one publication of the same study existed, the publication with the most complete data was included.
Studies were identified from MEDLINE (1950 to April, week 4, 2009), Embase (1980 to week 17, 2009), and The Cochrane Library (Cochrane Library, issue 3, 2009) (
Data were extracted without blinding to authorship, on the recruitment methods evaluated, the population setting, and the trial design, as well as risk of bias items such as randomisation, allocation concealment, blinding of outcome assessors, loss to follow up, and intention-to-treat analysis. These elements were each assessed separately using the method developed by the Cochrane Collaboration
The primary outcome of interest was consent rates for the different recruitment strategies. Because studies differed in definitions of consent rates, where possible we recalculated the consent rate of each recruitment method by dividing the number of participants exposed to the recruitment method who actually consented for clinical study participation by the total number of potential participants exposed to that method (see
Where possible we used relative risk (RR) and their 95% confidence intervals (CIs) to describe the effects of different strategies in individual recruitment trials. Where more than two strategies were used in a single recruitment trial, the numerator and denominator from the standard (control) recruitment strategy was divided by the number of intervention strategies for each comparison so that the control numbers would not be overrepresented
From 16,703 unique titles and abstracts, 396 articles were retrieved and 37 eligible publications identified (
Trial Type | Author | Year of Publication | Country of Trial | Health Problem Studied | Intervention Arms of RCT | Recruitment Strategy Studied | ||
Treatment | Du |
2008 | USA | Lung cancer | Mixed treatments (multiple trials) | Information provision | 26 | 126 |
Hutchison |
2007 | UK | Multiple cancers | Mixed treatments (multiple trials) | Information provision | 128 | 173 | |
Monaghan |
2006 | Multinational | BP control in diabetics | Antihypertensive versus placebo | Recruiter differences | 7,847 | 167 sites | |
Litchfield |
2005 | UK | Diabetes | Two insulin delivery systems | Recruiter differences | 73 | 80 | |
Kimmick |
2005 | USA | Multiple cancers | Mixed treatments (multiple trials) | Recruiter differences | 1,097 | unknown | |
Nystuen |
2004 | Norway | Absentee employees | Follow up versus standard care | Information provision | 97 | 703 | |
Donovan |
2003 | UK | Prostate cancer | Surgery versus radiotherapy versus monitoring | Recruiter differences | 103 | 150 | |
Coyne |
2003 | USA | Multiple cancers | Chemotherapy (multiple trials) | Information provision | 147 | 226 | |
Quinaux |
2003 | France | Breast cancer | Chemotherapies | Recruiter differences | 362 | unknown | |
Tworoger |
2002 | USA | Breast cancer | Aerobic exercises versus stretching | Information provision | 376 | 4,999 | |
Fleissig |
2001 | UK | Multiple cancers | Mixed treatments (multiple trials) | Recruiter differences | 205 | 265 (15 recruiters) | |
Miller |
1999 | USA | Depression | Psychotherapy versus antidepressants versus both | Recruiter differences | 50 | 347 | |
Cooper |
1997 | UK | Menorrhagia | Medical management versus surgery | Trial design | 187 | 273 | |
Berner |
1997 | USA | Gynaecological cancers | Mixed treatments (multiple trials) | Information provision | 9 | 120 | |
Aaronson |
1996 | The Netherlands | Multiple cancers | Chemotherapy (multiple trials) | Information provision | 146 | 346 | |
Wadland |
1990 | USA | Smoking | Nicotine gum versus standard care | Information provision | 52 | 104 | |
Simes |
1986 | Australia | Multiple cancers | Mixed treatments (multiple trials) | Information provision | 50 | 57 | |
Prevention | Leira |
2009 | USA | Aspiration pneumonia | Ranitidine versus placebo | Information provision | 52 | 100 |
Mandelblatt |
2005 | USA | Breast cancer | Tamoxifen versus Raloxifene | Information provision | 325 | 450 | |
Avenell |
2004 | UK | Fractures | Vitamins versus placebo/no treatment | Trial design | 367 | 538 | |
Ford |
2004 | USA | Multiple cancers | Screening tests versus standard care | Information provision | 376 | 12,400 | |
Hemminki |
2004 | Estonia | Postmenopausal health risks | Hormone replacement versus placebo/ no treatment | Trial design | 1,823 | 4,295 | |
Larkey |
2002 | USA | cardiovascular disease, cancer and osteoporosis | Hormone replacement therapy and dietary modification and calcium and vitamin D supplements | Recruiter differences | 13 | 34+ | |
Kendrick |
2001 | UK | Home safety | Safety equipment versus usual care | Information provision | 374 | 2,397 | |
Kiernan |
2000 | USA | Healthy diet | Additional goal setting techniques versus standard care | Information provision | 9 | 561 | |
Welton |
1999 | UK | menopausal symptoms and osteoporosis | Hormone replacement therapies versus placebo | Trial design | 150 | 492 (438) | |
Rogers |
1998 | USA | Risk for life threatening illness | Follow up versus standard care | Trial design | 44 | 57 | |
Valanis |
1998 | USA | Lung cancer | Vitamins versus placebo | Information provision | 451 | 22,546 | |
Mock trial | Halpern |
2004 | USA | Hypertension | Different hypertensives | Incentives+trial design | 66–94 | 142 |
Ellis |
2002 | Australia | Breast cancer | Chemotherapy versus Tamoxifen | Information provision | 26 | 180 | |
Martinson |
2000 | USA | Smoking cessation and prevention | Peer, mail, and phone contacts versus standard care | Incentives | 1,560 | 4,046 | |
Wragg |
2000 | UK | Postmenopausal health risks | Hormone replacement versus placebo | Information provision | 22 | 50 | |
Myles |
1999 | Australia | Anaesthesia for surgery | Experimental drug versus standard care | Trial design | 429 | 770 | |
Weston |
1997 | Canada | Premature labour | Induced labour versus expectant management | Information provision | 43 | 90 | |
Gallo |
1995 | Italy | Hypothetical disease | Experimental drug versus standard drug | Trial design | 1,620 | 2,035 | |
Llewellyn-Thomas |
1995 | Canada | Bowel cancer | Chemotherapy versus monitoring | Information provision | 52 | 102 | |
Simel |
1991 | USA | Variable presenting health problems | Standard versus new medication | Trial design | 55 | 100 | |
Total | 18,812 | 59,354+ |
Studies showed a statistically significant difference in consent rates between recruitment strategies.
BP, blood pressure.
There were 23 parallel group RCTs, six quasi-RCTs (including one using paired data), and eight cluster RCTs. Of the 37 included recruitment trials, only 12 studies (32%) had clear allocation concealment, two (4%) specified blinding of outcome assessors (no study had blinding of participants as this would have been difficult to achieve), 15 (40%) recorded loss to follow-up information, and 14 (38%) used intention-to-treat analysis (see
Trial Type | Author | Type Of RCT | Allocation Concealment | Blinding of Outcome Assessors | Loss to Follow Up Mentioned | Intention-to-Treat Analysis | Quality Items |
Prevention | Avenell |
Parallel | Yes | No | Yes | Yes | 3 |
Prevention | Rogers |
Parallel | Yes | Yes | No | Yes | 3 |
Treatment | Monaghan |
Cluster RCT | Yes | Unclear | Unclear | Yes | 2 |
Treatment | Hutchison |
Parallel | Yes | Unclear | Unclear | Yes | 2 |
Treatment | Cooper |
Parallel | Yes | No | No | Yes | 2 |
Treatment | Tworoger |
Parallel | Unclear | Unclear | Yes | Yes | 2 |
Treatment | Coyne |
Cluster RCT | Unclear | No | Yes | Yes | 2 |
Treatment | Du |
Parallel | Unclear | Yes | Yes | No | 2 |
Prevention | Kendrick |
Parallel | Yes | No | Yes | Unclear | 2 |
Prevention | Hemminki |
Parallel | Yes | No | Unclear | Yes | 2 |
Prevention | Ford |
Parallel | Unclear | No | Yes | Yes | 2 |
Prevention | Leira |
Parallel | No | Unclear | Yes | Yes | 2 |
Mock trial | Weston |
Parallel | Yes | No | Yes | Unclear | 2 |
Mock trial | Ellis |
Parallel | Yes | No | Yes | Unclear | 2 |
Mock trial | Llewellyn-Thomas |
Parallel | Yes | No | Yes | No | 2 |
Mock trial | Martinson |
Cluster RCT | Yes | No | Unclear | Yes | 2 |
Treatment | Donovan |
Parallel | Yes | No | No | No | 1 |
Treatment | Wadland |
Parallel | Unclear | No | Yes | Unclear | 1 |
Treatment | Aaronson |
Parallel | Unclear | No | Yes | Unclear | 1 |
Treatment | Berner |
Quasi-RCT | No | Unclear | Yes | Unclear | 1 |
Treatment | Nystuen |
Parallel | No | Unclear | Unclear | Yes | 1 |
Prevention | Larkey |
Cluster RCT | Unclear | No | Yes | No | 1 |
Prevention | Valanis |
Parallel | Unclear | No | No | Yes | 1 |
Prevention | Welton |
Quasi-RCT | No | No | Yes | Unclear | 1 |
Mock trial | Simel |
Parallel | Unclear | No | No | Yes | 1 |
Treatment | Quinaux |
Cluster RCT | Unclear | Unclear | Unclear | Unclear | 0 |
Treatment | Kimmick |
Cluster RCT | Unclear | Unclear | Unclear | Unclear | 0 |
Treatment | Litchfield |
Cluster RCT | Unclear | Unclear | Unclear | Unclear | 0 |
Treatment | Fleissig |
Cluster RCT | Unclear | No | No | Unclear | 0 |
Treatment | Simes |
Parallel | No | No | No | Unclear | 0 |
Treatment | Miller |
Quasi-RCT | No | No | No | Unclear | 0 |
Prevention | Kiernan |
Parallel | Unclear | No | No | Unclear | 0 |
Prevention | Mandelblatt |
Quasi-RCT | No | No | Unclear | Unclear | 0 |
Mock trial | Gallo |
Parallel | Unclear | No | No | Unclear | 0 |
Mock trial | Myles |
Parallel | Unclear | No | No | Unclear | 0 |
Mock trial | Wragg |
Quasi-RCT | Unclear | No | No | Unclear | 0 |
Mock trial | Halpern |
Paired data | No | No | Unclear | Unclear | 0 |
Of the 37 included studies, 17 assessed treatment comparisons, 11 were prevention studies, and nine mock studies (where participants declared their willingness to participate in a trial but no actual trial occurred).
There were 66 different types of recruitment strategies that were broadly categorised into four groups: novel trial designs (nine studies), recruiter differences (eight studies), incentives (two studies), and provision of trial information (19 studies), with one study looking at both novel trial design and incentives
Avenell and Hemminki
RR, intervention recruitment strategy/standard recruitment strategy. Used total number/number of intervention strategies to calculate RR, so that the number of patients on standard strategies were not overrepresented; S, random assignment for participants, standard care for nonparticipants; 2, patients are told physician believes the experimental drug may be superior. Increased chance of receiving the experimental drug after consenting; 3, patients are told that they are allowed to increase or decrease their chance of receiving the new experimental drug after consenting; 4, experimental drug for participants, standard care for nonparticipants; 5, standard drug for participants, experimental drug for nonparticipants; 6, random assignment for participants, choice of either treatments for nonparticipants.
Study | Standard Recruitment Strategy | Consent Rate (95% CI) | Experimental Recruitment Strategies | Consent Rate (95% CI) | RR (95% CI) | ||
Myles |
One-sided informed consent |
84/151 | 56% (48–64) | One-sided physician modified |
91/150 | 61% (52–69) | 1.10 (0.80–1.50) |
One-sided patient modified |
85/150 | 57% (48–65) | 1.03 (0.75–1.41) | ||||
Prerandomised to experimental drug |
90/169 | 53% (45–61) | 0.96 (0.70–1.33) | ||||
Prerandomised to standard drug |
79/149 | 53% (45–61) | 0.96 (0.69–1.33) | ||||
Gallo |
One-sided informed consent |
521/622 | 84% (81–87) | Prerandomised to experimental drug |
642/730 | 88% (86–90) | 1.05 (0.98–1.12) |
Prerandomised to standard drug |
156/307 | 51% (45–56) | 0.60 (0.53–0.69) |
||||
Two-sided informed consent |
301/376 | 80% (76–84) | 0.95 (0.88–1.03) | ||||
Avenell |
Standard placebo-controlled design | 233/358 | 65% (60–70) | Nonblinded trial design | 134/180 | 74% (67–81) | 1.14 (1.02–1.28) |
Hemminki |
Standard placebo-controlled design | 796/2,136 | 37% (35–39) | Nonblinded trial design | 1,027/2159 | 48% (46–50) | 1.28 (1.19–1.37) |
Rogers |
Opting-in consent for participation | 24/32 | 75% (57–89) | Opting-out consent for nonparticipation | 20/25 | 80% (59–93) | 1.07 (0.81–1.41) |
Cooper |
Standard informed consent | 97/138 | 70% (62–78) | Partially randomised patient preference |
90/135 | 67% (58–75) | 0.95 (0.81–1.11) |
Simel |
Consent for trial of usual treatment versus new treatment that may work twice as fast | 35/52 | 67% (53–80) | Consent for trial of usual treatment versus new treatment that may work half as fast | 20/48 | 41% (28–57) | 0.62 (0.42–0.91) |
Halpern |
10% risk of adverse effects | 26/64 | 41% (29–54) | 20% risk of adverse effects | 23/64 | 36% (24–49) | 1.08 (0.59–2.00) |
10% risk of adverse effects | 26/64 | 41% (29–54) | 30% risk of adverse effects | 18/64 | 28% (18–41) | 1.44 (0.72–2.89) | |
20% risk of adverse effects | 23/64 | 36% (24–49) | 30% risk of adverse effects | 18/64 | 28% (18–41) | 1.33 (0.65–2.72) | |
Halpern |
10% risk of adverse effects | 33/64 | 52% (39–64) | 20% risk of adverse effects | 26/64 | 41% (29–54) | 1.31 (0.77–2.22) |
10% risk of adverse effects | 33/64 | 52% (39–64) | 30% risk of adverse effects | 23/64 | 36% (24–49) | 1.42 (0.81–2.46) | |
20% risk of adverse effects | 26/64 | 41% (29–54) | 30% risk of adverse effects | 23/64 | 36% (24–49) | 1.08 (0.59–2.00) | |
Halpern |
10% risk of adverse effects | 35/64 | 55% (42–67) | 20% risk of adverse effects | 29/64 | 45% (33–58) | 1.20 (0.74–1.94) |
10% risk of adverse effects | 35/64 | 55% (42–67) | 30% risk of adverse effects | 25/64 | 39% (27–52) | 1.38 (0.82–2.33) | |
20% risk of adverse effects | 29/64 | 45% (33–58) | 30% risk of adverse effects | 25/64 | 39% (27–52) | 1.15 (0.66–2.02) | |
Halpern |
10% assigned to placebo | 21/62 | 34% (22–47) | 30% assigned to placebo | 20/62 | 32% (21–45) | 1.10 (0.55–2.21) |
10% assigned to placebo | 21/62 | 34% (22–47) | 50% assigned to placebo | 19/62 | 31% (20–44) | 1.10 (0.55–2.21) | |
30% assigned to placebo | 20/62 | 32% (21–45) | 50% assigned to placebo | 19/62 | 31% (20–44) | 1.00 (0.49–2.06) | |
Halpern |
10% assigned to placebo | 27/62 | 44% (31–57) | 30% assigned to placebo | 25/62 | 40% (28–54) | 1.08 (0.61–1.90) |
10% assigned to placebo | 27/62 | 44% (31–57) | 50% assigned to placebo | 23/62 | 37% (25–50) | 1.17 (0.65–2.10) | |
30% assigned to placebo | 25/62 | 40% (28–54) | 50% assigned to placebo | 23/62 | 37% (25–50) | 1.08 (0.59–1.99) | |
Halpern |
10% assigned to placebo | 28/62 | 45% (33–58) | 30% assigned to placebo | 26/62 | 42% (30–55) | 1.08 (0.61–1.90) |
10% assigned to placebo | 28/62 | 45% (33–58) | 50% assigned to placebo | 27/62 | 44% (31–57) | 1.00 (0.58–1.73) | |
30% assigned to placebo | 26/62 | 42% (30–55) | 50% assigned to placebo | 27/62 | 44% (31–57) | 0.93 (0.53–1.64) | |
Welton |
Standard placebo-controlled design | 65/218 | 30% (24–36) | Noninferiority trial design | 85/218 | 39% (33–46) | 1.31 (1.01–1.70) |
RR, experimental recruitment strategy/standard recruitment strategy. Used total number/number of experimental strategies to calculate RR, so that standard was not overrepresented. Halpern's study used each participant more than once.
Random assignment for participants, standard care for nonparticipants.
Patients told physician believes the experimental drug may be superior. Increased chance of receiving the experimental drug after consenting.
Patients are told that they are allowed to increase or decrease their chance of receiving the new experimental drug after consenting.
Experimental drug for participants, standard care for nonparticipants.
Standard drug for participants, experimental drug for nonparticipants.
Studies showed a statistically significant difference in consent rates between recruitment strategies.
Random assignment for participants, choice of either treatments for nonparticipants.
Patients could choose to be randomised or choose their own treatment, but only those who chose to be randomised were compared with standard treatment.
Gallo and Myles (both for mock studies) compared standard randomisation (random assignment for all participants and standard care for nonparticipants) with different types of randomisation designs
Cooper compared standard consent with partially randomised patient preference where patients could choose to be randomised or choose their own (medical or surgical) treatment
Rogers compared “opting in” with “opting out”
Simel compared consenting to a clinical study assessing standard medication versus a new medication that worked twice as fast with a clinical study comparing standard medication with a new medication that worked half as fast as the standard medication
Halpern
Eight recruitment trials compared recruiter differences (see
RR, intervention recruitment strategy/standard recruitment strategy.
Study | Standard Recruitment Strategy | Consent Rate (95% CI) | Experimental Recruitment Strategies | Consent Rate (95% CI) | RR (95% CI) | ||
Donovan |
Recruitment by urologist | 53/75 | 71% (59–81) | Recruitment by nurse | 50/75 | 67% (55–77) | 0.94 (0.76–1.17) |
Miller |
Recruitment by senior investigator | 28/162 | 17% (12–24) | Recruitment by research assistant | 22/185 | 12% (8–17) | 0.69 (0.41–1.15) |
Fleissig |
Standard consent, doctors not aware of patients' personal preferences | 96/130 | 74% (65–81) | Doctors shown patient's responses to questionnaire regarding personal preferences and trial participation before recruiting patients for trial | 109/135 | 81% (73–87) | 1.09 (0.96–1.25) |
Litchfield |
Paper-based data recording | 28/28 screened | 100% (88–100) | Internet data capture | 45/52 screened | 87% (74–94) | 0.87 (0.78–0.96) |
Quinaux |
Centres not monitored | 186/34 centres | Monitored centres | 176/34 centres | |||
Larkey |
Recruiters not trained | 0/28 recruiters | Recruiters trained | 13/28 recruiters | |||
Kimmick |
Standard recruitment, website access and periodic notification | 777 (year 1)+384 (year 2) = 1,161 | Additional seminar, educational materials, list of available protocols, email and mail reminders, and case discussion seminars for recruiters | 691 year 1)+384 (year 2) = 1,075 | |||
Monaghan |
Usual communication | 37 (median) per site at 82 sites | Frequent email contact and individual feedback about recruitment to the recruiter | 37.5 (median) per site at 85 sites |
RR, experimental recruitment strategy/standard recruitment strategy.
Studies showed a statistically significant difference in consent rates between recruitment strategies.
Donovan and Miller compared recruiter roles (doctor versus nurse RR 0.94, 95% CI 0.76–1.17
Litchfield compared internet-derived database handling with paper-based database handling
Martinson and Halpern assessed incentives for increasing recruitment (see
RR, intervention recruitment strategy/standard recruitment strategy. Used total number/number of intervention strategies to calculate RR, so that the number of patients on standard strategies were not overrepresented; S, random assignment for participants, standard care for nonparticipants; 1, small incentives (US$2 prepaid cash incentive); 2, larger incentive (US$15) contingent on response; 3, US$200 prize draw.
Study | Standard Recruitment Strategy | Consent Rate (95% CI) | Experimental Recruitment Strategies | Consent Rate (95% CI) | RR (95% CI) | ||
Martinson |
No incentives | 288/996 | 29% (26–32) | US$2 small prepaid cash | 423/1,021 | 41% (38–45) | 1.43 (1.19–1.72) |
Large cash incentives contingent on response (US$15) | 452/1,021 | 44% (41–47) | 1.53 (1.28–1.84) |
||||
US$200 prize draw | 397/1008 | 39% (36–42) | 1.36 (1.13–1.64) |
||||
Halpern |
US$100 | 26/64 | 41% (29–54) | US$1,000 | 33/64 | 52% (39–64) | 0.76 (0.45–1.30) |
US$100 | 26/64 | 41% (29–54) | US$2,000 | 35/64 | 55% (42–67) | 0.72 (0.43–1.21) | |
US$1,000 | 33/64 | 52% (39–64) | US$2,000 | 35/64 | 55% (42–67) | 0.94 (0.60–1.48) | |
Halpern |
US$100 | 23/64 | 36% (24–49) | US$1,000 | 26/64 | 41% (29–54) | 0.92 (0.30–1.70) |
US$100 | 23/64 | 36% (24–49) | US$2,000 | 29/64 | 45% (33–58) | 0.80 (0.45–1.43) | |
US$1,000 | 26/64 | 41% (29–54) | US$2,000 | 29/64 | 45% (33–58) | 0.87 (0.50–1.51) | |
Halpern |
US$100 | 18/64 | 28% (18–41) | US$1,000 | 23/64 | 36% (24–49) | 0.75 (0.37–1.53) |
US$100 | 18/64 | 28% (18–41) | US$2,000 | 25/64 | 39% (27–52) | 0.69 (0.35–1.39) | |
US$1,000 | 23/64 | 36% (24–49) | US$2,000 | 25/64 | 39% (27–52) | 0.92 (0.50–1.70) | |
Halpern |
US$100 | 21/62 | 34% (22–47) | US$1,000 | 27/62 | 44% (31–57) | 0.79 (0.43–1.45) |
US$100 | 21/62 | 34% (22–47) | US$2,000 | 28/62 | 45% (33–58) | 0.70 (0.43–1.45) | |
US$1,000 | 27/62 | 44% (31–57) | US$2,000 | 28/62 | 45% (33–58) | 1.00 (0.58–1.73) | |
Halpern |
US$100 | 20/62 | 32% (21–45) | US$1,000 | 25/62 | 40% (28–54) | 0.77 (0.40–1.48) |
US$100 | 20/62 | 32% (21–45) | US$2,000 | 26/62 | 42% (30–55) | 0.77 (0.40–1.48) | |
US$1,000 | 25/62 | 40% (28–54) | US$2,000 | 26/62 | 42% (30–55) | 1.00 (0.56–1.80) | |
Halpern |
US$100 | 19/62 | 31% (20–44) | US$1,000 | 23/62 | 37% (25–50) | 0.83 (0.42–1.64) |
US$100 | 19/62 | 31% (20–44) | US$2,000 | 27/62 | 44% (31–57) | 0.71 (0.38–1.36) | |
US$1,000 | 23/62 | 37% (25–50) | US$2,000 | 27/62 | 44% (31–57) | 0.86 (0.48–1.54) |
RR, experimental recruitment strategy/standard recruitment strategy. Used total number/number of experimental strategies to calculate RR, so that standard was not overrepresented. Halpern's study used each participant more than once.
Studies showed a statistically significant difference in consent rates between recruitment strategies.
The Halpern study assessed the effect of variations in monetary incentives on the willingness to participate in a number of mock clinical studies (of varying trial designs that was mentioned earlier). Patients' willingness to participate increased as the payment level increased from US$100 to US$2,000 irrespective of the risk of adverse effect and risk of being assigned to placebo, although the difference was not statistically significant.
Nineteen recruitment trials compared different methods of providing information to participants, including how the information was presented and what information was provided (see
RR, intervention recruitment strategy/standard recruitment strategy. Used total number/number of intervention strategies to calculate RR, so that the number of patients on standard strategies were not overrepresented; S, standard informed consent; B, bulk mailing; 1, enhanced recruitment letter and screening by African American interviewer; 2, enhanced recruitment letter, screening by African American interviewer and baseline information collected via telephone interview; 3, enhanced recruitment letter, screening by African American interviewer and church-based project sessions; 4, bulk mailing with letter; 5, first-class mailing; 6, first-class mailing with letter.
Study | Standard Recruitment Strategy | Consent Rate (95% CI) | Experimental Recruitment Strategies | Consent Rate (95% CI) | RR (95% CI) | ||
Kendrick |
Standard informed consent (mailing) | 157/1,194 | 13% (11–15) | Additional home safety questionnaire | 217/1,203 | 18% (16–20) | 1.37 (1.14–1.66) |
Kiernan |
Standard informed consent (mailing of flyer) | 0/191 | 0% (0–2) | Additional personal letter (combination of general letter+Hispanic specific letter) | 9/370 | 2% (1–5) | 9.83 (0.58–168.04) |
Valanis |
Standard informed consent (mailing) | 225/11,273 | 2% (2–6) | Advanced postcard 1 wk prior to mailing of recruitment packet | 226/11,273 | 2% (2–2) | 1.0 (0.84–1.21) |
Nystuen |
Standard informed consent (mailing) | 42/347 | 12% (9–16) | Additional reminder phone call for nonresponders | 55/356 | 15% (12–19) | 1.28 (0.88–1.85) |
Ford |
Standard informed consent (mailing)+screening |
95/3,297 | 3% (2–4) | Enhanced recruitment letter+screening by African American interviewer | 78/3,079 | 3% (2–3) | 0.87 (0.58–1.31) |
Enhanced recruitment letter+screening by African American interviewer+baseline information collected via telephone interview | 87/3,075 | 3% (2–3) | 0.97 (0.65–1.45) | ||||
Enhanced recruitment letter+screening by African American interviewer+church-based project sessions | 116/2,949 | 4% (3–5) | 1.35 (0.92–1.99) | ||||
Tworoger |
Bulk mailing no letters | 86/1,250 | 7% (6–8) | Bulk mailing with letter | 87/1,251 | 7% (6–9) | 1.00 (0.67–1.50) |
First class mailing no letters | 102/1,249 | 8% (7–10) | 1.17 (0.79–1.75) | ||||
First class mailing with letters | 101/1,249 | 8% (7–10) | 1.16 (0.78–1.73) | ||||
Leira |
Standard informed consent | 25/50 | 50% (36–65) | Advanced notification with phone and fax | 27/50 | 54% (39–68) | 1.08 (0.74–1.57) |
Llewellyn-Thomas |
Tape recording of trial information | 21/50 | 42% (28–57) | Interactive computer program for participants | 31/50 | 62% (47–75) | 1.48 (1.00–2.18) |
Weston |
Standard informed consent | 17/48 | 35% (22–51) | Additional video about the health condition | 26/42 | 62% (46–76) | 1.75 (1.11–2.74) |
Berner |
Standard informed consent (verbal) | 4/50 | 7% (2–19) | Additional written cancer-specific information | 4/56 | 7% (2–17) | 0.89 (0.24–3.38) |
Ellis |
Standard informed consent | 14/42 | 33% (20–50) | Additional education booklet on trials | 12/41 | 29% (16–46) | 0.88 (0.46–1.66) |
Du |
Standard informed consent | 10/63 | 16% (8–27) | Additional video about clinical trials | 16/63 | 25% (15–38) | 1.60 (0.79–3.25) |
Hutchison |
Standard informed consent | 66/87 | 76% (66–84) | AVPI tool to explain about trials, video+DVD/CD | 62/86 | 72% (61–81) | 0.95 (0.80–1.13) |
Coyne |
Standard informed consent | 93/137 | 68% (59–76) | Easy-to-read consent statement | 67/89 | 75% (65–84) | 1.11(0.94–1.31) |
Wadland |
Patients reading trial information | 25/53 | 47% (33–61) | Study coordinator reading and explaining the study to patients | 27/51 | 53% (39–67) | 1.12 (0.76–1.65) |
Aaronson |
Standard informed consent | 78/90 | 87% (78–93) | Additional phone-based contact with oncology nurse | 68/90 | 76% (65–84) | 0.87 (0.76–1.01) |
Mandelblatt |
Standard informed consent (brochure) | 147/218 | 67% (61–74) | Additional brief educational session and discussion about the trial | 178/232 | 77% (71–82) | 1.14 (1.01–1.28) |
Simes |
Total disclosure | 23/28 | 82% (63–94) | Individual approach | 27/29 | 93% (77–99) | 1.13 (0.93–1.38) |
Wragg |
Explicit information |
8/26 | 31% (14–52) | Ambiguous information |
14/24 | 58% (37–78) | 1.90 (0.97–3.70) |
RR, experimental recruitment strategy/standard recruitment strategy. Used total number/number of experimental strategies to calculate RR, so that standard was not overrepresented.
Studies showed a statistically significant difference in consent rates between recruitment strategies.
Standard informed consent and screening (used total number/number of experimental strategies to calculate RR, so that standard was not overrepresented).
Provides the current best estimates of effect of the experimental treatment.
Emphasises the current state of uncertainty.
There were six recruitment trials that related to mailing of recruitment material for the clinical study. The methods used to enhance recruitment were the addition of: a questionnaire that focused on the health problem studied (Kendrick
Leira compared standard consent (being invited to participate in the clinical study when the investigators met the patient during helicopter retrievals) with advanced notification of the clinical study with telephone and faxing of informed consent documents prior to arrival of investigators in the helicopter
Three recruitment trials looked at increasing participants' understanding of the clinical trial process, which did not appear to affect recruitment
Three recruitment trials assessed strategies that aim to increase participants' understanding of their underlying condition. Llewellyn-Thomas compared tape recorded reading of clinical study information with an interactive computer program where participants (who were oncology patients receiving radiation therapy) were actively involved in the information search process
Three recruitment trials compared standard consent with additional personal contact with research staff (a study coordinator reading and explaining the clinical study, Wadland
There were two recruitment trials assessing framing of recruitment information. In Simes' 1986 trial of recruitment for a cancer treatment study
Trials of recruitment strategies have evaluated all steps in the recruitment process, including different methods of trial design, randomisation, provision of information, and recruiter differences. In this systematic review, we found that strategies that increased potential participants' awareness of the health problem being studied by engaging them in the learning process significantly increased consent rates (both for “real” and mock trials). These strategies included the addition of a questionnaire that focused on the health problem studied and additional educational sessions, videos, and interactive programs about the diseases studied
The recruitment trials on how recruitment information was provided (the technique of information presentation, how information was framed, who presented the information, and when the information was presented) did not show a difference between strategies, demonstrating that how or when the information was presented or who presented the information did not influence recruitment, but rather the information provided. A recent study (which was published after completion of our last search update) also showed that publicity about the trial did not increase recruitment
Although a previous observational study showed that framing of recruitment information to emphasise uncertainty enhanced recruitment
In our review, one recruitment trial identified that a noninferiority clinical study (with active treatment arms) had higher consent rates compared with a placebo-controlled clinical study. This finding is consistent with previous findings that patients preferred “trials with all active arms to placebo-controlled trials”
The inclusion of recruitment trials of recruitment to mock clinical studies enabled assessment of recruitment strategies, which for equity reasons would be difficult to compare (such as different randomisation designs, different monetary incentives). Some strategies may be acceptable when used in isolation, but inappropriate when more than one are used within the same clinical study: for example mock trials that tested the hypothesis that potential participants are more willing to participate in a study if they had an increased chance of receiving the experimental treatment is a strategy that has been adopted by many vaccine and other clinical studies in the belief that potential participants are more likely to participate if they believed they had a higher chance of receiving the (desirable) experimental treatment. However, we found that increasing the likelihood of receiving the experimental treatment
As results of mock clinical studies are based on whether participants are willing to enrol in a clinical study (rather than whether they actually consented), extrapolation to real clinical studies may not be realistic. Stated “willingness to participate” and actual participation may also differ. In the recruitment trial comparing standard consent to the addition of a video explaining clinical trial information and the health problem studied for a mock clinical study, although statistically more participants from the video group were willing to enrol in the clinical study, this number became not statistically significant 2 wk later
Although there have been two previous systematic reviews on strategies to enhance recruitment to research
Our findings are consistent with the health belief model that people are more likely to adopt a health behaviour (such as participation in a clinical study) if they perceive they are at risk of a significant health problem
Because of major differences in recruitment methods, populations, and types of clinical studies that were recruiting as well as outcomes measured, we did not combine the results statistically in a meta-analysis. In many of the smaller recruitment trials, the failure to find a significant difference in consent rates could be related to the sample size (type II error). There may also be publication bias. However, as more than 70% (27/37) of the included studies had a nonsignificant result, we are hopeful that publication bias may be minimal. Given that the interventions we are considering are of noncommercial value we would suggest that publication bias may be less likely than for other interventions.
The majority of the included trials were conducted in developed countries, with a substantial proportion in the US. We acknowledge that developed countries' health systems may be very different from those of less-developed countries and hence the results of this systematic review may not be generalizable to other countries.
The main limitation of the study, due to the prolonged conduct of the study (from 2000 to 2009), was that the search strategy had to be modified with subsequent search updates owing to changes in MEDLINE Mesh heading definitions. Because of these changes (and the large number of titles and abstracts searched), the reason for exclusion of each study cannot be provided. The abstract of the first version of this systematic review (which included nonrandomised studies owing to the lack of randomised recruitment trials on the subject at the time) was published in conference proceedings in 2002
Our systematic review of recruitment strategies for enhancing participation in clinical RCTs has identified a number of effective and ineffective recruitment strategies. Grouped together, the statistically significant strategies either engaged participants in learning about the health problem being studied and its impact on their health or else informed participants of the treatment they have been randomised to receive (nonblinded trial design). However, as there was differential loss to follow up in the different treatment arms with nonblinded trial design, this trial design is likely to jeopardise the validity of the results. The use of monetary incentives may also increase recruitment, but as this was tested in a mock trial, and as another mock trial did not show any difference in consent rates between different amounts of monetary incentives, this finding needs to be interpreted with caution.
Future RCTs of recruitment strategies that engaged participants in the learning process using various methods of delivering the recruitment material compared with standard recruitment may confirm the effectiveness of this concept. This research may be particularly useful for testing strategies that expose large number of potential participants to recruitment information such as interactive internet strategies.
PRISMA checklist.
(0.07 MB DOC)
Thanks to Ravinder Summan, Rebecca George, Phyllis Butow, Mike Jones, Gabrielle Williams, Premala Sureshkumar, Tamara Borysko, and others at Centre for Kidney Research for their help in preparation of this manuscript.
confidence interval
randomised controlled trial
relative risk