The Closeout Process for a Clinical Trial Terminated Early for Lagging Enrollment and Inadequate Follow-up

Muth, K; Yu, Eunice; Alston, Beverly; Ellenberg, Jonas H.

doi:10.1016/s0197-2456(00)00111-2

Cited by 10 publications

(11 citation statements)

References 1 publication

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“…As a result, the DCC lead nurse coordinator and project manager made several trips to sites to provide training for new staff and substantial assistance with closeout activities. Fortunately, these trips had been expected based on work by others [6] so the DCC made budgeting accommodations. Risk-based monitoring and central statistical monitoring have received increased attention where efforts focus on risks to the “most critical data elements and processes necessary to achieve study objectives” [22] and identifying problem sites[23, 24].…”

Section: Discussionmentioning

confidence: 99%

“…The site investigator certified that the last Study A participant’s images were de-identified and transferred to the IAC, the final images had resulted, and all study materials were removed from the radiology department. Staff from the Data Coordinating Center made final monitoring visits (FMV) to all sites[6] in a two month period to ensure all milestones had been reached. They also provided assistance when there was lack of progress in any aspects of the closeout process largely due to staff attrition.…”

Section: Closeout Of the Clinical Sitesmentioning

confidence: 99%

“…[1–3] Authors have made recommendations on designing closeouts to ensure patient safety, follow-up, and timely publications for trials reaching their expected end[1–4] while others have described the aspects of shutting down studies earlier than planned. [5–7] Specific recommendations entail having a common closing date[1] and post-treatment follow-up[1, 4], preparing patients psychologically for trial end[1], updating patient contact information[1, 2], getting staff input about operational details and feasibility of closeout plans[3], including plans for early termination[3, 6], ensuring adequate training for data collection and entry[2], allowing for adaptable strategies[2] and flexibility in staff roles[6], keeping communication flowing with sites[2, 6], and allowing time and personnel for closeout[6]. However, when closeout has not been planned early, minimal guidance exists to help investigators prioritize design and conduct issues during the end of a long-term trial.…”

Section: Introductionmentioning

confidence: 99%

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Closeout of the HALT-PKD trials

Moore

Spillane

Simon

et al. 2015

Contemporary Clinical Trials

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Background The HALT Polycystic Kidney Disease Trials Network consisted of two randomized, double blind, placebo-controlled trials among patients with autosomal dominant polycystic kidney disease. The trials involved 5–8 years of participant follow-up with interventions in blood pressure and antihypertensive therapy. We provide a framework for designing and implementing closeout near the end of a trial while ensuring patient safety and maintaining scientific rigor and study morale. Methods We discuss issues and resolutions for determining the last visit, tapering medications, and unblinding of participants to study allocation and results. We also discuss closure of clinical sites and Data Coordinating Center responsibilities to ensure timely release of study results and meeting the requirements of regulatory and funding authorities. Results Just over 90% of full participants had a 6-month study visit prior to their last visit preparing them for trial closeout. Nearly all patients wanted notification of study results (99%) and treatment allocation (99%). All participants were safely tapered off study and open label blood pressure medications. Within 6 months, the trials were closed, primary papers published, and 805 letters distributed to participants with results and allocation. DCC obligations for data repository and clinicaltrials.gov reporting were completed within 12 months of the last study visit. Conclusions Closeout of our trials involved years of planning and significant human and financial resources. We provide questions for investigators to consider when planning closeout of their trials with focus on (1) patient safety (2) dissemination of study results and (3) compliance with regulatory and funding responsibilities.

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Section: Discussionmentioning

confidence: 99%

Section: Closeout Of the Clinical Sitesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Closeout of the HALT-PKD trials

Moore

Spillane

Simon

et al. 2015

Contemporary Clinical Trials

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“…Several factors can influence the decision to terminate an ongoing clinical trial including ethical concerns, changes in accepted clinical practice that make the continuation of a clinical trial unwise, or reaching a positive or negative statistical endpoint earlier than anticipated ( Table 1). The discontinuation of a clinical trial can be prompted by either the investigators or the study sponsor with or without the input of independent data and safety monitoring boards [1]. Investigator-specific considerations are generally more pertinent for single-center trials ( Table 1) , but may also influence multicenter trials, particularly if the investigative site in question has contributed a significant number of patients to the clinical trial [2].…”

Section: Lessons Learned From Prematurely Terminated Clinical Trials mentioning

confidence: 99%

Lessons learned from prematurely terminated clinical trials

Sica

2001

Current Science Inc

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Controlled clinical trials in cardiovascular disease are the cornerstone for therapeutic advances in this field of medicine. Since the introduction of the concept of controlled clinical trials, there has been substantial progress in the design, conduct, and analysis of such studies. A growing awareness of ethical issues emerging from such trials has led to increased public and investigator scrutiny, and the routine requirement for interim data analysis. A benefit of such interim analysis is that either an entire clinical trial or a specific treatment limb can be stopped if the observed findings warrant premature termination. For example, highly positive findings, as were noted in the Heart Outcomes Prevention Evaluation (HOPE) study, led to its closure about 1 year early after 4.5 years of treatment. Alternatively, the doxazosin treatment limb of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and the amlodipine treatment limb of the African-American Study of Kidney Disease and Hypertension (AASK) were stopped early because of negative findings. Finally, economic considerations can enter into the decision to close a study early as was the case in the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) trial. Most such decisions rely heavily on information obtained from independent data and safety monitoring boards. Such boards ensure patient safety by providing an unbiased ongoing review of data, which would otherwise be unavailable until a study's completion. Early termination of a clinical trial can have important clinical implications and, in particular, can redirect patterns of clinical practice.

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“…The discontinuation of a clinical trial can be prompted by either the investigator(s), the study sponsor, or by mutual agreement. This decision can be reached with or without the input of a properly constituted independent Data and Safety Monitoring Board 1 . Investigator‐specific considerations are generally more relevant for single‐center trials (Table) but May also influence multicenter trials, particularly if the investigative site in question has been a heavy enroller in the clinical trial 2 …”

Section: Selected Negative Reasons For Discontinuing a Clinical Trialmentioning

confidence: 99%

Premature Termination of Clinical Trials—Lessons Learned

Sica

2002

J of Clinical Hypertension

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Controlled clinical trials in cardiovascular disease are the cornerstone for therapeutic advances in this field of medicine. Since the introduction of the concept of controlled clinical trials there has been substantial progress in the design, conduct, and analysis of such studies. A growing awareness of ethical issues emerging from such trials has heightened public awareness, increased investigator scrutiny, and reinforced the need for interim data analysis. A benefit of such interim analyses is that either an entire clinical trial or a specific treatment limb can be stopped if the observed findings argue for premature termination. For example, highly positive findings, as were noted in the HOPE Study (Heart Outcomes Prevention Evaluation), led to its being stopped after 4.5 years of treatment, which was 1 year early. Alternatively, the doxazosin treatment limb of the ALLHAT (Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial) and the amlodipine treatment limb of A ASK (African American Study of Kidney Disease and Hypertension) were stopped early because of negative findings with each respectively. Finally, economic considerations can enter into the decision to close a study early as was the case in the CONVINCE (Controlled Onset Verapamil Investigation of Cardiovascular End Points) trial. Most such decisions rely heavily on information obtained from independent data and safety monitoring boards. Such boards ensure patient safety by providing an unbiased ongoing review of data, which would otherwise be unavailable until a study's completion. Early termination of a clinical trial can have important clinical implications and, in particular, can redirect patterns of clinical practice.

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The Closeout Process for a Clinical Trial Terminated Early for Lagging Enrollment and Inadequate Follow-up

Cited by 10 publications

References 1 publication

Closeout of the HALT-PKD trials

Closeout of the HALT-PKD trials

Lessons learned from prematurely terminated clinical trials

Premature Termination of Clinical Trials—Lessons Learned

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