Invisible Barriers to Clinical Trials: The Impact of Structural, Infrastructural, and Procedural Barriers to Opening Oncology Clinical Trials

Dilts, David M.; Sandler, Alan

doi:10.1200/jco.2005.05.0104

Cited by 140 publications

(141 citation statements)

References 5 publications

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“…Study start-up has been examined in more detail in oncology clinical trials. [12][13][14] These studies also observed that administrative processes, including review of a protocol by multiple IRBs, lengthen study start-up times. Some institutions require completion of the contract execution process before submission of a protocol to their local IRB.…”

Section: Adherence and Retentionmentioning

confidence: 97%

Analysis of start-up, retention, and adherence in ALS clinical trials

Atassi¹,

Yerramilli-Rao²,

Szymonifka³

et al. 2013

Neurology

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Objective: To investigate predictors of trial start-up times, high attrition, and poor protocol adherence in amyotrophic lateral sclerosis (ALS) trials.Methods: Retrospective analysis of start-up times, retention, and protocol adherence was performed on 5 clinical studies conducted by the Northeast ALS Consortium and 50 ALS clinical trials identified by PubMed search. Predictors of start-up times were estimated by accelerated failure time models with random effects. Predictors of retention and protocol deviations were estimated by mixed-model logistic regression.Results: Median times for contract execution and institutional review board (IRB) approval were 105 days and 125 days, respectively. Contract execution was faster at sites with more ongoing trials (p 5 0.005), and more full-time (p 5 0.006) and experienced (p , 0.001) coordinators. IRB approval was faster at sites with more ongoing trials (p 5 0.010) and larger ALS clinics (p 5 0.038). Site activation after IRB approval was faster at sites with more full-time (p 5 0.038) and experienced (p , 0.001) coordinators. Twenty-two percent of surviving participants withdrew before completing the trial. Better participant functional score at baseline was an independent predictor of trial completion (odds ratio 1.29, p 5 0.002) and fewer protocol deviations (odds ratio 0.86, p 5 0.030).Conclusion: Delays in IRB review contribute the most to prolonged trial start-up times, and these timelines are faster in sites with more experienced staff. Strategies to improve protocol adherence and participants' retention may include enrolling people at early disease stages. The translation of basic research to clinical practice depends on the conduct of well-designed and efficient clinical trials. Delays in study start-up, high participant attrition, and poor adherence to the study protocol reduce trial validity and inflate the timelines and costs of drug development. In published clinical trials, enrollment and retention data are routinely reported; however, factors affecting study start-up times, retention, and adherence to the protocol are rarely mentioned. 1,2Conducting efficient clinical trials involves completing study start-up processes in a timely manner. This includes execution of the site contracts, obtaining institutional review board (IRB) approvals, and completing protocol, pharmacy, and outcomes trainings. Delays in the study start-up process can extend trial duration and costs, threaten trial feasibility, and delay answering important clinical questions.The internal validity of a clinical trial depends largely on good conduct including retention and maintaining good protocol adherence (i.e., complying with the study protocol). In addition, high attrition requires larger sample sizes to maintain statistical power and subsequently inflates trial duration and costs. 3,4 Amyotrophic lateral sclerosis (ALS) is a rare neurologic disorder that has many potential therapies currently in development.5 With a small patient population and limited funds, it is critical

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Section: Adherence and Retentionmentioning

confidence: 97%

Analysis of start-up, retention, and adherence in ALS clinical trials

Atassi¹,

Yerramilli-Rao²,

Szymonifka³

et al. 2013

Neurology

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“…1 The slow development of protocols, redundant scientific and ethical reviews, and protocol requirements that hinder enrollment contribute to the inferior conduct of clinical trials in academic centers. [2][3][4] In 2006, the Clinical and Translational Science Award (CTSA) program of the National Institutes of Health (NIH) was developed to support a national consortium of biomedical research institutions to accelerate progress in clinical research. The NIH subsequently requested proposals for work that would improve processes related to the development, approval, activation, enrollment, and completion of clinical trials.…”

Section: Introductionmentioning

confidence: 99%

“…Division of Pulmonology, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 2 Cystic Fibrosis Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle, WA, USA; 3 Cystic Fibrosis Foundation, Bethesda, MD, USA; 4 University of Pittsburgh, Pittsburgh, PA, USA; 5 The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Health Care System, Lebanon, NH, USA; 6 University of Washington, Seattle, WA, USA.…”

mentioning

confidence: 99%

Highly Effective Cystic Fibrosis Clinical Research Teams: Critical Success Factors

et al. 2014

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BACKGROUND:Bringing new therapies to patients with rare diseases depends in part on optimizing clinical trial conduct through efficient study start-up processes and rapid enrollment. Suboptimal execution of clinical trials in academic medical centers not only results in high cost to institutions and sponsors, but also delays the availability of new therapies. Addressing the factors that contribute to poor outcomes requires novel, systematic approaches tailored to the institution and disease under study. OBJECTIVE: To use clinical trial performance metrics data analysis to select high-performing cystic fibrosis (CF) clinical research teams and then identify factors contributing to their success. DESIGN: Mixed-methods research, including semistructured qualitative interviews of high-performing research teams. PARTICIPANTS: CF research teams at nine clinical centers from the CF Foundation Therapeutics Development Network. APPROACH: Survey of site characteristics, direct observation of team meetings and facilities, and semistructured interviews with clinical research team members and institutional program managers and leaders in clinical research. KEY RESULTS: Critical success factors noted at all nine high-performing centers were: 1) strong leadership, 2) established and effective communication within the research team and with the clinical care team, and 3) adequate staff. Other frequent characteristics included a mature culture of research, customer service orientation in interactions with study participants, shared efficient processes, continuous process improvement activities, and a businesslike approach to clinical research. CONCLUSIONS: Clinical research metrics allowed identification of high-performing clinical research teams. Site visits identified several critical factors leading to highly successful teams that may help other clinical research teams improve clinical trial performance.

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“…It had also commissioned Dr. David Dilts to undertake a systems analysis of clinical trial approval and implementation to determine where the bottlenecks to clinical trial delivery were most acute [3]. Contract negotiations could take more than a year, and there was no difference in the time needed to finalize contracts by phase of study.…”

Section: Improved Delivery Of Cancer Drug Clinical Trialsmentioning

confidence: 99%