Contemporary Clinical Trials

Editorial Board

2009-11-01

Attrition and retention in clinical trials by ethnic origin

Haleh Sangi-Haghpeykar, Hannah M. Meddaugh, Hao Liu, Placido Grino — 2009-08-21

Abstract: Context: Common perceptions exist within the medical community that retention of Hispanics in clinical trials is difficult, albeit little data is available to support this conviction.Methods: A total of 541 randomly selected charts from closed clinical trials between 2000 and 2006 were reviewed. Records were from participating institutions in Texas Medical Center, Houston, and targeted diseases of high prevalence, specifically, breast cancer, prostate cancer, and chronic obstructive pulmonary disease (COPD)/asthma.Findings: Overall, 259 participants (48%) completed the trial they were enrolled in (44% whites, 69% Hispanics, 51% blacks; p<.05). Within pediatric trials, whom all were pulmonary patients, retention rates were higher among Hispanics than whites (adjusted odds ratio [OR]=7.49, 95% confidence interval [CI]=1.15–58.03, p=.04). Among adults, patient's ethnicity was unrelated to study completion. All associations were adjusted for possible confounders. Reasons for not completing a trial varied by ethnicity: “patient withdrawing consent” was more common among whites (51.4%) than Hispanics (21.7%) or blacks (26.2%) (p<.05). Hispanics were more inclined to be withdrawn from the trial by the investigator (43.5%) than were whites (24%, p=.04), mostly due to non-compliance with the study protocol.Conclusions: Hispanic parents of children with COPD may be more likely to complete a trial than parents of non-Hispanic whites. Among adults, Hispanics had similar completion rates as compared to whites. Culturally sensitive, multi-factorial approaches maybe imperative to increasing patient engagement in clinical trials.

Measurement and predictors of adherence in a trial of HSV suppressive therapy in Tanzania

2009-09-01

Abstract: This study estimates adherence and identifies predictors of good adherence among 1305 Tanzanian women participating in a randomised, double-blind, placebo-controlled trial of HSV suppressive therapy to reduce HIV incidence or genital HIV shedding. Women were randomised to acyclovir 400mg BD or placebo and followed every three months for 12–30months. Adherence was assessed by tablet counts. Random urine samples, collected between 6 and 24months, were tested for acyclovir. At 12, 24 and 30month visits, 56%, 52% and 54% of women on treatment had adherence ≥90%, respectively. Factors independently associated with good adherence (taking ≥90% of tablets in the preceding 3-months) included older age, understanding trial concepts at enrolment, living >2years in the screening site, receiving an unannounced tablet check visit, using oral contraception at screening, living in the same site and house as the previous visit, accessing VCT during the trial, recent malaria and not having a positive pregnancy test. Overall, 55% of urine samples from women randomised to acyclovir had detectable acyclovir. Additional, tailored adherence strategies may be needed for younger, more mobile women and those who have not used oral contraception, which may sensitise them to daily tablet-taking. Use of biomarkers may alert investigators to adherence problems.

Issues in the design of a randomized noninferiority clinical trial of telemental health psychotherapy for rural combat veterans with PTSD

2009-07-21

Abstract: This methodological article provides a description of the design, methods, and rationale of the first prospective, noninferiority designed randomized clinical trial evaluating the clinical and cost implications of delivering an evidence-based cognitive-behavioral group intervention specifically treating posttraumatic stress disorder (PTSD) with a trauma-focused intervention via video teleconferencing (VTC). PTSD is a prevalent mental health problem found among returning Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) military populations. These returning military personnel often live in rural areas and therefore have limited access to care and specialized psychological treatments. In the field of mental health, telemental health (TMH) technology has introduced a potential solution to the persistent problem of access to care in remote areas. This study is enrolling approximately 126 returning veterans with current combat-related PTSD who are receiving services through the Veteran Administration (VA) mental health care clinics on 4 Hawaiian Islands. Cognitive Processing Therapy (CPT), an empirically supported manualized treatment for PTSD, is being delivered across 9 cohorts. Participants are assigned to either the experimental VTC condition or the in-person control condition. Assessments measuring clinical, process, and cost outcomes are being conducted at baseline, mid-treatment, post-treatment, and 3 and 6months post-treatment. The study employs a noninferiority design to determine if the group treatment delivered via VTC is as good as the traditional in-person modality. In addition, a cost analysis will be performed in order to compare the cost of the 2 modalities. Novel aspects of this trial and specific challenges are discussed.

Sensitivity of dose-finding studies to observation errors

Sarah Zohar, John O'Quigley — 2009-07-31

Abstract: The purpose of Phase I designs is to estimate the MTD (maximum tolerated dose, in practice a dose with some given acceptable rate of toxicity) while, at the same time, minimizing the number of patients treated at doses too far removed from the MTD. Our purpose here is to investigate the sensitivity of conclusions from dose-finding designs to recording or observation errors. Certain toxicities may go undetected and, conversely, certain non-toxicities may be incorrectly recorded as dose-limiting toxicities. Recording inaccuracies would be expected to have an influence on final and within trial recommendations and, in this paper, we study in greater depth this question. We focus, in particular on three designs used currently; the standard ‘3+3’ design, the grouped up-and-down design [M. Gezmu, N. Flournoy, Group up-and-down designs for dose finding. Journal of Statistical Planning and Inference 2006; 136 (6): 1749–1764.] and the continual reassessment method (CRM, [J. O'Quigley, M. Pepe, L. Fisher, Continual reassessment method: a practical design for phase 1 clinical trials in cancer. Biometrics 1990; 46 (1): 33–48.]). A non-toxicity incorrectly recorded as a toxicity (error of first kind) has a greater influence in general than the converse (error of second kind). These results are illustrated via figures which suggest that the standard ‘3+3’ design in particular is sensitive to errors of the second kind. Such errors can have a very important impact on drug development in that, if carried through to the Phase 2 and Phase 3 studies, we can significantly increase the probability of failure to detect efficacy as a result of having delivered an inadequate dose.

Design of the Value of Urodynamic Evaluation (ValUE) trial: A non-inferiority randomized trial of preoperative urodynamic investigations

2009-08-11

Abstract: Background and purpose: Urodynamic studies (UDS) are routinely obtained prior to surgery for stress urinary incontinence (SUI) despite a lack of evidence that UDS information has an actual impact on outcome. The primary aim of this non-inferiority randomized clinical trial is to determine whether women with symptomatic, uncomplicated SUI who undergo only a basic office evaluation (BOE) prior to SUI surgery (No UDS arm) have non-inferior treatment outcomes compared to women who have BOE and UDS (UDS arm). Secondary aims are: 1) to determine how often physicians use preoperative UDS results to alter clinical and surgical decision-making, 2)to compare the amount of improvement in incontinence outcomes, and 3) to determine the incremental cost and utility of performing UDS compared with not performing UDS.Methods: After an initial basic office evaluation, women planning surgery for uncomplicated SUI who consent to study participation will be randomized to receive preoperative UDS or No UDS. Treatment will be planned and performed by the surgeon utilizing all the data available to them. We will compare results from the basic office evaluation (No UDS) with results from the basic office evaluation and preoperative UDS.Results: The primary outcome will be measured at 12months using responses to the Urogenital Distress Inventory and the Patient Global Index-Improvement.Conclusions: Randomized trials comparing the effects of different diagnostic alternatives on treatment outcomes pose study design challenges. A non-inferiority design is appropriate when comparing a less invasive and less expensive alternative with a standard of care approach.

SMART trial: A randomized clinical trial of self-monitoring in behavioral weight management-design and baseline findings

2009-09-04

Abstract: Background: The primary form of treatment for obesity today is behavioral therapy. Self-monitoring diet and physical activity plays an important role in interventions targeting behavior and weight change. The SMART weight loss trial examined the impact of replacing the standard paper record used for self-monitoring with a personal digital assistant (PDA). This paper describes the design, methods, intervention, and baseline sample characteristics of the SMART trial.Methods: The SMART trial used a 3-group design to determine the effects of different modes of self-monitoring on short- and long-term weight loss and on adherence to self-monitoring in a 24-month intervention. Participants were randomized to one of three conditions (1) use of a standard paper record (PR); (2) use of a PDA with dietary and physical activity software (PDA); or (3), use of a PDA with the same software plus a customized feedback program (PDA+FB).Results: We screened 704 individuals and randomized 210. There were statistically but not clinically significant differences among the three cohorts in age, education, HDL cholesterol, blood glucose and systolic blood pressure. At 24months, retention rate for the first of three cohorts was 90%.Conclusions: To the best of our knowledge, the SMART trial is the first large study to compare different methods of self-monitoring in a behavioral weight loss intervention and to compare the use of PDAs to conventional paper records. This study has the potential to reveal significant details about self-monitoring patterns and whether technology can improve adherence to this vital intervention component.

Recruiting minorities where they receive care: Institutional barriers to cancer clinical trials recruitment in a safety-net hospital

Galen Joseph, Daniel Dohan — 2009-07-22

Abstract: Introduction: Most research on the barriers to recruitment of ethnic and racial minorities focuses on patient factors. The purpose of this exploratory case study was to examine how institutional factors impacted recruitment and enrollment in a public hospital clinic frequented by minority patients.Methods: We used ethnographic methods (observations of patient–provider interactions and semi-structured interviews) to document and explain how a number of institutional barriers hindered trials enrollment in a public hospital outpatient breast cancer clinic.Results: We identified two categories of institutional barriers: (1) organizational climate, and (2) research specific resources. Organizational climate included qualities of the clinic and hospital such as the clinic structure (clinic hours, patient assignment method), the interdisciplinary care team, the lack of continuity of care, and competing provider priorities of clinical care, teaching, and research. Research specific resources included: staff, funds and institutional status to facilitate opening a range of trials; and linguistically and literacy-appropriate research resources.Conclusion: Although we cannot determine from our qualitative data the relative impact of different kinds of barriers (e.g. patient, provider, institutional barriers), our data highlights the need to address the role of institutional barriers in efforts to improve minority recruitment to clinical trials. Recruiting participants in safety-net settings may be a reasonable strategy for increasing accrual of ethnic and racial minority patients to cancer clinical trials. However, our qualitative data suggest that while opening protocols for accrual at minority-serving institutions may signal nominal access to trials, achieving substantive access may require further steps to overcome substantial institutional barriers.