Patient- and trial-specific barriers to participation in cardiovascular randomized clinical trials.

Published on Feb 19, 2013in Journal of the American College of Cardiology20.589
· DOI :10.1016/J.JACC.2012.10.046
Seth S. Martin50
Estimated H-index: 50
(Johns Hopkins University),
Fang-Shu Ou28
Estimated H-index: 28
(UNC: University of North Carolina at Chapel Hill)
+ 4 AuthorsTracy Y. Wang69
Estimated H-index: 69
(Duke University)
Objectives The purpose of this study was to quantitatively examine the association of patient- and trial-specific factors with participation in cardiovascular randomized clinical trials. Background Randomized clinical trials are central to evidenced-based medicine, but low patient participation rates and potentially modifiable barriers are not well understood. Methods At a large U.S. academic health system, we examined screening logs from December 1, 2005, to February 28, 2011, from 15 cardiovascular randomized clinical trials. We identified 655 patients who were screened and potentially eligible for participation in at least 1 trial. We used multivariable Poisson regression to quantify the risk of not participating in a trial associated with patient- and trial-specific factors. Results The median age was 63 years (interquartile range: 54 to 72), 35% were women, and the median Charlson Index was 2 (interquartile range: 1 to 5). Forty-two percent of patients did not participate in a trial. In multivariable regression (C-Index 0.85), trial-specific factors strongly associated with not participating included intensive trial-related testing (relative risk [RR]: 1.89; 95% confidence interval [CI]: 1.63 to 2.20) and anticipated trial participation >6 months (RR: 4.10; 95% CI: 2.30 to 7.29). Patient-specific factors associated with not participating included older age (RR: 1.23; 95% CI: 1.11 to 1.36, per 10-year increase if age ≥65 years), out-of-state residence (RR: 1.26; 95% CI: 1.04 to 1.54), and female sex (RR: 1.17; 95% CI: 1.01 to 1.35). Race was not associated with participation. Conclusions While patient-specific factors were associated with not participating in cardiovascular trials, longer trial duration and intensive trial-related testing were most strongly associated with risk for patients not participating. Innovative trial designs fostering convenience may most enhance trial participation.
📖 Papers frequently viewed together
16 Authors (Qi Zhou)
8 Citations
98 Citations
589 Citations
#1Pierluigi Tricoci (Duke University)H-Index: 23
#2Zhen Huang (Duke University)H-Index: 16
Last. Kenneth W. Mahaffey (Duke University)H-Index: 113
view all 42 authors...
In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER number, NCT00527943.).
596 CitationsSource
#1Chee Tang Chin (Durham University)H-Index: 9
#2Tracy Y. Wang (Durham University)H-Index: 69
Last. Eric D. Peterson (Durham University)H-Index: 25
view all 12 authors...
Background Platelet inhibition is critical in reducing both short- and long-term atherothrombotic risks after acute myocardial infarction (MI), especially among patients managed with percutaneous coronary intervention (PCI). Currently available antiplatelet medications, including adenosine diphosphate (ADP) receptor inhibitors, have demonstrated variability in efficacy and safety in clinical trials, yet few studies have examined contemporary “real-world” approaches to platelet inhibition and ass...
50 CitationsSource
#1Jeffrey L. Probstfield (UW: University of Washington)H-Index: 73
#2Robert L. FryeH-Index: 37
CLINICAL TRIALS AND THE CONSEQUENT BENEFITS TO society are in jeopardy in the United States because of a decline in the ability to recruit patients in a timely manner to trials addressing key clinical issues. Current initiatives (eg, the Clinical Trials Transformation Initiative and the proposed National Center for Advancing Translational Sciences) and the recent Institute of Medicine report each recognize that successful recruitment and retention of participants in clinical trials is critical f...
54 CitationsSource
#1John H. Alexander (Duke University)H-Index: 81
#2Renato D. Lopes (Duke University)H-Index: 87
Last. Lars Wallentin (Uppsala University)H-Index: 150
view all 34 authors...
The addition of apixaban, at a dose of 5 mg twice daily, to antiplatelet therapy in high-risk patients after an acute coronary syndrome increased the number of major bleeding events without a significant reduction in recurrent ischemic events. (Funded by Bristol-Myers Squibb and Pfizer; APPRAISE-2 number, NCT00831441.).
802 CitationsSource
#1Esther S.H. Kim (Cleveland Clinic)H-Index: 21
#2Thomas P. CarriganH-Index: 2
Last. Venu Menon (Cleveland Clinic)H-Index: 57
view all 3 authors...
Objectives The aim of this study was to describe international enrollment and participation in National Institutes of Health (NIH)–sponsored cardiovascular randomized controlled trials (RCTs). Background RCTs provide the evidence base for major societal guidelines and profoundly influence patient care in the United States. Increased international involvement in clinical trials has been observed, but the rate of international enrollment in NIH-sponsored cardiovascular RCTs has not been described....
24 CitationsSource
The report by Kim et al. ([1][1]) in this issue of the Journal documents the increasingly widespread phenomenon of the “offshoring” of clinical research—in this case, clinical trials conducted in foreign countries despite being funded by U.S. taxpayers, administered through grants and
36 CitationsSource
#1Christopher M. O'Connor (Duke University)H-Index: 145
#2Randall C. Starling (Cleveland Clinic)H-Index: 102
Last. Robert M. Califf (Duke University)H-Index: 65
view all 57 authors...
A b s t r ac t Background Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. Methods We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, a...
969 CitationsSource
#1Samer S. Najjar (MedStar Washington Hospital Center)H-Index: 63
#2Sunil V. Rao (Duke University)H-Index: 84
Last. Robert A. Harrington (Duke University)H-Index: 139
view all 20 authors...
Context Acute ST-segment elevation myocardial infarction (STEMI) is a leading cause of morbidity and mortality. In experimental models of MI, erythropoietin reduces infarct size and improves left ventricular (LV) function. Objective To evaluate the safety and efficacy of a single intravenous bolus of epoetin alfa in patients with STEMI. Design, Setting, and Patients A prospective, randomized, double-blind, placebo-controlled trial with a dose-escalation safety phase and a single dose (60 000 U o...
184 CitationsSource
#1G. Michael Felker (Duke University)H-Index: 94
#2Kerry L. Lee (Duke University)H-Index: 139
Last. Christopher M. O'Connor (Duke University)H-Index: 145
view all 22 authors...
Among patients with acute decompensated heart failure, there were no significant differences in patients’ global assessment of symptoms or in the change in renal function when diuretic therapy was administered by bolus as compared with continuous infusion or at a high dose as compared with a low dose. (Funded by the National Heart, Lung, and Blood Institute; number, NCT00577135.)
1,026 CitationsSource
#1Seth W. Glickman (UNC: University of North Carolina at Chapel Hill)H-Index: 19
#2Adanma NdubuizuH-Index: 2
Last. Charles B. Cairns (UNC: University of North Carolina at Chapel Hill)H-Index: 41
view all 7 authors...
AbstractPersons with limited English proficiency (LEP) constitute a growing portion of the U.S. population, yet they are underrepresented in clinical research. This inherently limits the societal benefits of the research and its generalizability to ethnic populations living in the United States. To
21 CitationsSource
Cited By52
#1Spurthy Dharanikota (FIU: Florida International University)H-Index: 2
#2Cynthia LeRouge (FIU: Florida International University)H-Index: 20
Last. Matthew Thompson (UW: University of Washington)H-Index: 64
view all 5 authors...
Background: A rise in the recent trend of self-managing health using consumer health technologies highlights the importance of efficient and successful consumer health technology trials. Trials are particularly essential to support large-scale implementations of consumer health technologies, such as smartphone-supported home tests. However, trials are generally fraught with challenges, such as inadequate enrollment, lack of fidelity to interventions, and high dropout rates. Understanding the rea...
#1Ellen Murphy (UCC: University College Cork)H-Index: 1
#2Aoife O'Keeffe (UCC: University College Cork)
Last. Frances Shiely (UCC: University College Cork)H-Index: 16
view all 6 authors...
BACKGROUND Randomised controlled trials (RCTs) are the gold standard for demonstrating the efficacy of new therapies. However, issues of external validity often affect result application to real-world settings. Using registries to conduct RCTs is a reasonably new practice, but is appealing because it combines the benefits of both observational studies and RCTs. There is limited literature on patient motivators, barriers, and consent to registries for conducting RCTs. The purpose of our study was...
#1Justin A. Ezekowitz (U of A: University of Alberta)H-Index: 69
#2Robert J. Mentz (Duke University)H-Index: 53
Last. Lothar Roessig (Bayer)H-Index: 22
view all 12 authors...
Background: Randomized controlled trials (RCTs) often target enrollment of patients with demographics and outcomes less representative of the broader population of interest. To provide context for ...
#1Edgardo Rodríguez-Torres (UPR-RP: University of Puerto Rico, Río Piedras)
#2Margarita M. González-Pérez (University of Puerto Rico, Medical Sciences Campus)
Last. Clemente Díaz-Pérez (University of Puerto Rico, Medical Sciences Campus)
view all 3 authors...
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...
#1Sera Whitelaw (McMaster University)H-Index: 3
#2Kristen Sullivan (McMaster University)H-Index: 3
Last. Harriette G.C. Van SpallH-Index: 16
view all 9 authors...
AIMS To evaluate temporal trends in the enrolment of females in randomized controlled trials (RCTs) of heart failure with reduced ejection fraction (HFrEF) published in high-impact journals, and assess RCT characteristics associated with under-enrolment. METHODS AND RESULTS We searched MEDLINE, EMBASE and CINAHL for studies published from January 2000 to May 2019 in journals with impact factor ≥10. We included RCTs that recruited adults with HFrEF. We used a 20% threshold below the sex distribut...
10 CitationsSource
#1Cheryl Carcel (USYD: University of Sydney)H-Index: 14
#2Mathew J. Reeves (MSU: Michigan State University)H-Index: 77
Abstract: The under-representation of women in clinical trials is a commonly recognized and seemingly intractable problem in many different areas of clinical medicine. Discrepancies in the enrollme...
4 CitationsSource
#1Shantrel Canidate (UF: University of Florida)H-Index: 4
#2Christa L. Cook (UCF: University of Central Florida)H-Index: 10
Last. Robert L. Cook (UF: University of Florida)H-Index: 55
view all 7 authors...
Despite efforts by the NIH to enhance the participation of women and minorities in clinical research, women with HIV continue to remain underrepresented in alcohol intervention research. The purpose of this study is to better understand the reasons why women with HIV and hazardous drinking participated in the WHAT-IF? study and to discuss their experience (positive or negative) in the study. The WHAT-IF? study was a randomized clinical trial that evaluated pharmacotherapy for a reduction in drin...
3 CitationsSource
#1John J. Warner (UTSW: University of Texas Southwestern Medical Center)H-Index: 17
#2Hannah L. Crook (UW: University of Washington)H-Index: 3
Last. Nancy Brown (AHA: American Heart Association)H-Index: 5
view all 12 authors...
The pipeline of new cardiovascular drugs is relatively limited compared with many other clinical areas. Challenges causing lagging drug innovation include the duration and expense of cardiovascular clinical trials needed for regulatory evaluation and approvals, which generally must demonstrate noninferiority to existing standards of care and measure longer-term outcomes. By comparison, there has been substantial progress in cardiovascular device innovation. There has also been progress in cardio...
5 CitationsSource
#1Alexander C. Fanaroff (UPenn: University of Pennsylvania)H-Index: 13
#2Marat Fudim (Duke University)H-Index: 22
Last. Renato D. Lopes (Duke University)H-Index: 87
view all 6 authors...
Abstract Background Clinical guideline documents reflect the evidence supporting clinical practice, but few recommendations in cardiovascular guidelines are supported by evidence from randomized controlled trials (RCTs), the highest level of evidence. Incentives for generating evidence from RCTs differ by topic of guideline recommendation, and it is uncertain whether evidence supporting guideline recommendations differs based on the topic of the recommendation. Methods We abstracted recommendati...
1 CitationsSource