Background
Clinical trials that end prematurely (or “terminate”) raise financial, ethical, and scientific concerns. The extent to which the results of such trials are disseminated and the reasons for termination have not been well characterized.
Methods and Findings
A cross-sectional, descriptive study of terminated clinical trials posted on the ClinicalTrials.gov results database as of February 2013 was conducted. The main outcomes were to characterize the availability of primary outcome data on ClinicalTrials.gov and in the published literature and to identify the reasons for trial termination. Approximately 12% of trials with results posted on the ClinicalTrials.gov results database (905/7,646) were terminated. Most trials were terminated for reasons other than accumulated data from the trial (68%; 619/905), with an insufficient rate of accrual being the lead reason for termination among these trials (57%; 350/619). Of the remaining trials, 21% (193/905) were terminated based on data from the trial (findings of efficacy or toxicity) and 10% (93/905) did not specify a reason. Overall, data for a primary outcome measure were available on ClinicalTrials.gov and in the published literature for 72% (648/905) and 22% (198/905) of trials, respectively. Primary outcome data were reported on the ClinicalTrials.gov results database and in the published literature more frequently (91% and 46%, respectively) when the decision to terminate was based on data from the trial.
Conclusions
Trials terminate for a variety of reasons, not all of which reflect failures in the process or an inability to achieve the intended goals. Primary outcome data were reported most often when termination was based on data from the trial. Further research is needed to identify best practices for disseminating the experience and data resulting from terminated trials in order to help ensure maximal societal benefit from the investments of trial participants and others involved with the study.
BackgroundEthical evaluation of risk–benefit in clinical trials is premised on the achievability of resolving research questions motivating an investigation.ObjectiveTo determine the fraction and n...
Trials that are unregistered, unfinished, unpublished, unreachable, or simply irrelevant Randomized controlled trials are the gold standard tool for evaluating interventions. Nevertheless, the utility of this excellent tool is contingent on how it is used. Chapman and colleagues (doi:10.1136/bmj.g6870) show this in a sample of 395 trials relevant to surgical practice that were registered in ClincialTrials.gov between 2008 and 2009.1 By the end of 2013, 21% were discontinued, 34% of those that we...
Last. Aneel Bhangu(University of Birmingham)H-Index: 37
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Objective To determine the rate of early discontinuation and non-publication of randomised controlled trials involving patients undergoing surgery. Design Cross sectional observational study of registered and published trials. Setting Randomised controlled trials of interventions in patients undergoing a surgical procedure. Data sources The ClinicalTrials.gov database was searched for interventional trials registered between January 2008 and December 2009 using the keyword “surgery”. Recruitment...
#2Russell B. McBride(ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 29
Last. Matthew D. Galsky(ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 63
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: The number and diversity of cancer therapeutics in the pipeline has increased over the past decade due to an enhanced understanding of cancer biology and the identification of novel therapeutic targets. At the same time, the cost of bringing new drugs to market and the regulatory burdens associated with clinical drug development have progressively increased. The finite number of eligible patients and limited financial resources available to evaluate promising new therapeutics represent rate-li...
Background Early termination of clinical trials due to low recruitment represents an understudied challenge for clinical research. We aimed to describe characteristics of cardiovascular trials terminated because of low recruitment and identify the major predictors of such early termination. Methods We reviewed all cardiovascular clinical trials (7,042 studies) registered in ClinicalTrials.gov from February 29, 2000, to January 17, 2013, and assessed information about trials that were completed a...
The 2007 Food and Drug Administration (FDA) Amendments Act expanded requirements for ClinicalTrials.gov, a public clinical trial registry maintained by the National Library of Medicine, mandating results reporting within 12 months of trial completion for all FDA-regulated medical products. Reporting of mandatory trial registration information on ClinicalTrials.gov is fairly complete, although there are concerns about its specificity; optional trial registration information is less complete.1- 4 ...
Importance The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear. Objectives To determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication. Design and Setting Retrospective cohort of RCTs based on archived protocols approved ...
Background The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration–approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. Methods and Findings We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of thes...
Last. Michael S. Lauer(NIH: National Institutes of Health)H-Index: 105
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From the Office of Special Projects of the Division of Cardiovascular Sciences (D.G., W.T.-P., A.M.), Office of Science and Technology (M.A.), the Clinical Applications and Prevention Branch of the Division of Cardiovascular Sciences (P.G.K.), and Office of the Director of the Division of Cardiovascular Sciences (M.S.L.) — all at the National Heart, Lung, and Blood Institute, Bethesda, MD. Address reprint requests to Dr. Lauer at 6701 Rockledge Dr., Rm. 8128, Bethesda, MD 20892, or at
Proactive and objective regulatory risk management of ongoing clinical trials is limited, especially when it involves the safety of the trial. We seek to prospectively evaluate the risk of facing adverse outcomes from standardized and routinely collected protocol data. We conducted a retrospective cohort study of 2860 Phase 2 and Phase 3 trials that were started and completed between 1993 and 2017 and documented in ClinicalTrials.gov. Adverse outcomes considered in our work include Serious or No...
Last. Clemente Díaz-Pérez(University of Puerto Rico, Medical Sciences Campus)
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Abstract null null Background null The demand for clinical trial participants is today one of the highest it has ever been and continues to increase. At the same time, subject recruitment continues to be problematic and the major reason for clinical trial premature terminations. The literature on clinical trial recruitment, which spans several decades and includes hundreds of studies, has an abundance of findings that can be synthesized by way of an overview to provide a well-informed and comple...
As of March 30 2021, over 5,193 COVID-19 clinical trials have been registered through Clinicaltrial.gov. Among them, 191 trials were terminated, suspended, or withdrawn (indicating the cessation of the study). On the other hand, 909 trials have been completed (indicating the completion of the study). In this study, we propose to study underlying factors of COVID-19 trial completion vs. cessation, and design predictive models to accurately predict whether a COVID-19 trial may complete or cease in...
#1Ann M. Davis(KU: University of Kansas)H-Index: 21
#2Paul M. Darden(University of Oklahoma Health Sciences Center)H-Index: 23
Last. Jeannette Y. Lee(University of Arkansas for Medical Sciences)H-Index: 70
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Abstract null null A significant percentage of clinical trials fail due to poor recruitment. Despite this, few studies exist to evaluate clinical trial recruitment strategies using a randomized approach in any population, and none exist to test recruitment strategies for trials involving children or rural populations. For clinical trials focused on weight control, evaluating retention and dose are extremely important, as poor retention can lead to biased samples and existing research shows that ...
#2Lisa Y. Lin(MEE: Massachusetts Eye and Ear Infirmary)H-Index: 1
Last. Jon F. Merz(UPenn: University of Pennsylvania)H-Index: 34
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We examine recruitment processes for 71 pragmatic and comparative effectiveness trials identified in a systematic review, using path analysis to examine rates of refusal to screen, test, and consent to trial participation. Our analysis suggests that refusal rates might be on net slightly higher if potential subjects are screened or asked to undergo physical eligibility tests, but this was not significant in our sample of trials (p = .11 by Mann-Whitney test). We find that rates of refusing to pr...
#1Aima A. Ahonkhai(VUMC: Vanderbilt University Medical Center)H-Index: 4
#2Usman J. Wudil(VUMC: Vanderbilt University Medical Center)H-Index: 2
Last. Muktar H. Aliyu(VUMC: Vanderbilt University Medical Center)H-Index: 33
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PURPOSE OF REVIEW Clinical trials represent a bedrock for measuring efficacy of interventions in biomedical research, but recruitment into clinical trials remains a challenge. Few data have focused on recruitment strategies from the perspective of clinical trial teams, especially in low- and middle-income countries (LMIC), where HIV is most prevalent. RECENT FINDINGS We summarized data from the literature and our experience with recruitment for the Renal Risk Reduction trial, aimed at reducing r...
Background: Ensuring adequate, informed, and timely participation in clinical trials is a multifactorial problem. We have previously developed a systematic, tailorable survey development approach that is informed by theory, can identify barriers and enablers to participation, and can suggest recruitment strategies to address these issues. In this study, we surveyed subscribers to the Canadian Breast Cancer Network (CBCN) in order to identify a comprehensive list of theory-informed barriers and e...
Background It is an ethical and scientific obligation to register each clinical trial, and report its results, accurately, comprehensively and on time. The WHO recognizes 17 public registries as Primary Registries, and has also introduced a set of minimal standards in the International Standards for Clinical Trial Registries (ISCTR) that primary registries need to implement. These standards are categorized into nine sections-Content, Quality and Validity, Accessibility, Unambiguous Identificatio...
ABSTRACT Participation in clinical trials is essential to bringing novel and innovative cancer treatments to the bedside but trials that specifically enroll Veterans are relatively few. Given the inherent differences between Veterans and the general United States population, we sought to investigate awareness of and attitudes toward clinical trials among Veterans diagnosed with cancer at a large, urban Veterans Administration Medical Center in Bronx, New York. The survey was administered in 2018...
Abstract: Objective Despite clear evidence showing that many clinical trials fail or are delayed because of poor patient recruitment, there is surprisingly little empirically supported guidance for trialists seeking to optimize their trial recruitment strategies. We propose that the challenges of recruitment can be better understood and addressed by thinking of research participation as one or more behaviours, subject to the same forces as other human behaviours. In this paper we describe an ada...
