Clinical trial implementation and recruitment: Lessons learned from the early closure of a randomized clinical trial

Cardiovascular and Pulmonary Medicine Branch, National Institutes of Health, Bethesda, MD 20892, United States.
Contemporary clinical trials (Impact Factor: 1.94). 12/2011; 33(2):291-7. DOI: 10.1016/j.cct.2011.11.018
Source: PubMed


The NHLBI-sponsored Sickle Cell Disease Clinical Research Network (SCDCRN) conducted a multi-center, acute intervention randomized clinical trial of two methods of Patient Controlled Analgesia for acute pain. This trial was terminated early due to low enrollment. We analyzed the perceived barriers and recruitment difficulties as reported by the coordinators and principal investigators.
Participating sites completed a missed eligibility log of subjects admitted in pain crisis throughout the study and a survey at the end of the trial. The survey covered site-specific factors, policies, and procedures in study implementation, recruitment strategies, and eligibility factors. The New England Research Institutes (NERI) collected de-identified surveys from 31 respondents at 29 of 31 participating sites.
From December 2009 to June 2010, 1116 patient encounters for SCD and pain occurred at participating institutions: 38 subjects were enrolled (14 pediatric and 24 adults) and 34 completed the trial, below the projected 278 subjects. Fourteen sites enrolled subjects and seventeen did not. Recruitment barriers included insufficient staff, subject ineligibility or in too much pain to consent, competing protocols, and concerns regarding pain control. Recruitment methods were referrals from urgent care, SCD clinics and in house databases. No use of media or outside physicians was reported.
We identified multiple barriers to patient accrual including short duration of enrollment period, protocol design, complex dosing schedule, requirement for staff availability during week-end and after hours, multiple departments' involvement, protocol acceptance, eligibility criteria, competing protocols, and limited staff. Each of these areas should be targeted for intervention in order to plan and conduct successful future clinical trials.

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    • "Clinical trials are essential for gaining and extending knowledge about new therapies, and sufficient patient enrollment in clinical trials is critical to fulfill their scientific objectives. Nevertheless, a number of trials have failed to achieve their target sample size within the original accrual period [1-3]. For such trials, extending the accrual period, modifying the eligibility criteria or, in the worst case scenario, prematurely closing the trial may be necessary. "
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    ABSTRACT: A number of clinical trials have encountered difficulties enrolling a sufficient number of patients upon initiating the trial. Recently, many screening systems that search clinical data warehouses for patients who are eligible for clinical trials have been developed. We aimed to estimate the number of eligible patients using routine electronic medical records (EMRs) and to predict the difficulty of enrolling sufficient patients prior to beginning a trial. Investigator-initiated clinical trials that were conducted at Kyoto University Hospital between July 2004 and January 2011 were included in this study. We searched the EMRs for eligible patients and calculated the eligible EMR patient index by dividing the number of eligible patients in the EMRs by the target sample size. Additionally, we divided the trial eligibility criteria into corresponding data elements in the EMRs to evaluate the completeness of mapping clinical manifestation in trial eligibility criteria into structured data elements in the EMRs. We evaluated the correlation between the index and the accrual achievement with Spearman's rank correlation coefficient. Thirteen of 19 trials did not achieve their original target sample size. Overall, 55% of the trial eligibility criteria were mapped into data elements in EMRs. The accrual achievement demonstrated a significant positive correlation with the eligible EMR patient index (r = 0.67, 95% confidence interval (CI), 0.42 to 0.92). The receiver operating characteristic analysis revealed an eligible EMR patient index cut-off value of 1.7, with a sensitivity of 69.2% and a specificity of 100.0%. Our study suggests that the eligible EMR patient index remains exploratory but could be a useful component of the feasibility study when planning a clinical trial. Establishing a step to check whether there are likely to be a sufficient number of eligible patients enables sponsors and investigators to concentrate their resources and efforts on more achievable trials.
    Full-text · Article · Dec 2013 · Trials
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    • "Important clinical outcomes may not be established due to insufficient numbers of study participants, and these studies are therefore an inappropriate use of participants and resources. Failure to enrol and retain participants may compromise the validity of study results [10]. Internal validity (or elimination of bias) is a requirement for external validity (or generalisability of study results to the larger target population), and RCTs protect against selection bias. "
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    ABSTRACT: Objectives: To describe recruitment to a randomised controlled trial of a 12-week (twice-weekly) supervised exercise programme for patients with peripheral arterial disease (PAD). PAD is a chronic, progressive disease with a significant cardiovascular and cerebrovascular risk burden, and exercise is an effective primary management approach. Method: Potential patients were identified from the Non-Invasive Vascular Laboratory records and invited to participate in the study. On successful completion of an incremental treadmill exercise test, patients were allocated at random to a control (usual care) or an exercise group. Results: Between November 2006 and June 2009, 548 patients were identified. Of the 156 patients who met the inclusion criteria, 40 (26%) declined to participate. Of the 71 patients who underwent exercise testing, 23 (32%) did not complete the test. The final enrolment number was 44 (44/156; 28%). Eleven patients (11/28; 39%) subsequently withdrew from the exercise programme. Conclusion: Recruitment to clinical trials of exercise presents significant challenges in the PAD population due to the presence of co-existing cardiovascular and cerebrovascular disease, a reluctance to exercise due to leg pain, and an acceptance of reduced mobility as part of ageing. Early identification in primary care before the onset of significant comorbidity may ameliorate some of these issues.
    Full-text · Article · Mar 2013 · Physiotherapy
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    • "Recruiting study participants is challenging for clinical, biomedical, and public health researchers, and the recruitment of racial and ethnic minorities is especially complex [1] [2]. In fact, there is a significant body of literature that documents barriers to minority participation in research [3] [4] [5] [6]. Despite these challenges , it is important for researchers to assemble representative samples in order to increase the generalizability of results and contribute to better health outcomes for minorities, which are critical steps in eliminating the persistent health disparities that exist between whites and racial and ethnic minority groups [7] [8]. "

    Full-text · Dataset · Mar 2013
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