Clinical trial implementation and recruitment: lessons learned from the early closure of a randomized clinical trial.
ABSTRACT 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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ABSTRACT: Management of the acute painful crisis (APC) of sickle cell disease (SCD) remains unsatisfactory despite advances in the understanding and management of acute pain in other clinical settings. One reason for this is an unsophisticated approach to the use of opioid analgesics for pain management. This applies to haematologists who are responsible for developing acute sickle pain management protocols for their patients, and to health care staff in the acute care setting. The objective of this article is to evaluate the evidence for use of opioids in APC management. We have highlighted the possibilities for improving management by using alternatives to morphine, and intranasal (IN) or transmucosal routes of administration for rapid onset of analgesia in the emergency department (ED). We suggest how experience gained in managing acute sickle pain in children could be extrapolated to adolescents and young adults. We have also questioned whether patients given strong opioids in the acute setting are being safely monitored and what resources are required to ensure efficacy, safety and patient satisfaction. We also identify aspects of care where there are significant differences of opinion, which require further study by randomized controlled trial.British Journal of Haematology 04/2014; · 4.94 Impact Factor
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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.Trials 12/2013; 14(1):426. · 2.21 Impact Factor
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ABSTRACT: Multiple recent Sickle Cell Disease studies have been terminated due to poor enrollment. We developed methods to overcome past barriers and utilized these to study the efficacy and safety of intravenous magnesium for vaso-occlusive crisis (VOC). We describe the methods of the Intravenous Magnesium in Sickle Vaso-occlusive Crisis (MAGiC) trial and discuss methods used to overcome past barriers. MAGiC was a multi-center randomized double-blind placebo-controlled trial of intravenous magnesium versus normal saline for treatment of VOC. The study was a collaboration between Pediatric Hematologists and Emergency Physicians in the Pediatric Emergency Care Applied Research Network (PECARN). Eligible patients were randomized within 12 hours of receiving intravenous opioids in the Emergency Department (ED) and administered study medication every 8 hours. The primary outcome was hospital length of stay. Associated plasma studies elucidated magnesium's mechanism of action and the pathophysiology of VOC. Health-related quality of life was measured. Site-, protocol-, and patient-related barriers from prior studies were identified and addressed. Limited study staff availability, lack of collaboration with the ED, and difficulty obtaining consent were previously identified barriers. Leveraging PECARN resources, forging close collaborations between Sickle Cell Centers and EDs of participating sites, and approaching eligible patients for prior consent helped overcome these barriers. Participation in the PECARN network and establishment of collaborative arrangements between Sickle Cell Centers and their affiliated EDs are major innovative features of the MAGiC study that allowed improved subject capture. These methods could serve as a model for future studies of VOCs. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.Pediatric Blood & Cancer 01/2014; · 2.35 Impact Factor