Gunn, Heather J.

ABSTRACT Objective This study compared the effects of phentermine‐topiramate‐ER (mid‐dose 7.5/46 mg) versus placebo on weight loss and cardiovascular disease (CVD) risk outcomes when used as an adjunct to a digitally enhanced lifestyle intervention (DELI). Methods We conducted a 12‐month, randomized, double‐blind, placebo‐controlled trial at a single tertiary academic center in the United States (June 2020–June 2022). Eighty participants with obesity (BMI ≥ 30 kg/m 2 ) were enrolled in the DELI program, consisting of in‐person and telehealth modalities, dietary and physical activity goals, and use of a smartphone application integrated with digital devices (Apple Watch and Bluetooth‐enabled weight scale and blood pressure monitor). Participants were randomized 1:1 to receive either phentermine‐topiramate‐ER ( n = 42) or placebo ( n = 38) in addition to the DELI. Results At 3 months, the phentermine‐topiramate group lost a mean of 10.82 kg versus 4.04 kg in the placebo group (mean difference −6.78 kg; p = 0.002). At 12 months, weight loss was 15.32 kg versus 5.85 kg, respectively (mean difference −9.48 kg; p < 0.001). Participants receiving phentermine‐topiramate‐ER experienced a 3.35% reduction in the estimated atherosclerotic CVD risk compared to baseline ( p = 0.004). Conclusions Phentermine‐topiramate‐ER, when combined with a DELI, produced significant and sustained weight loss and reduced CVD risk in adults with obesity. Trial Registration ClinicalTrials.gov : NCT04408586

PURPOSE Lack of race- and age-diversity in clinical trials adversely affects generalizability of trial results and equity of trial access. Research on barriers to representative accrual has focused on patient-level factors. We aimed to define site-level factors affecting the diversity of accrual to a multicenter clinical trial. METHODS Alliance 191901 (GETSET) is a national randomized controlled trial testing interventions to promote breast cancer endocrine therapy adherence, which oversamples Black women and those under age 50 years at 30% thresholds. A secondary study objective is to examine site-level factors associated with accrual of Black and younger participants. At 50% accrual to the parent study, we performed prespecified analyses of association between site characteristics (region, neighborhood racial composition, Alliance membership type, number of recent accruals to cooperative research group trials) and the proportion of Black patients and younger patients accrued. We also examined trajectories of accrual over time for race- and age-specified subgroups. RESULTS The analysis included 124 sites. Among 590 participants, 9.7% were Black, and 22.4% were age <50 years. Neither site type nor historical accrual volume was associated with Black participant recruitment. Southern sites recruited higher proportions of Black participants (19.0% v 7.3% for West, P < .001). Neighborhood racial composition was positively associated with recruitment of Black participants (16.2% at sites from highest Black composition v 1.4% in lowest, P < .01). Recruitment trajectories of Black participants were slower than target rates, whereas those among non-Black participants were faster. CONCLUSION Neighborhood composition and geographic region were predictors of proportions of Black participants accrued to A191901 sites, but site type and historical accrual volume were not. When trials must limit site selection, identifying sites based on neighborhood composition and geography may be an appropriate tool for increasing trial diversity.

Abstract Prevention trials in oncology are some of the most important cancer clinical trials that can be designed, implemented, analyzed, and interpreted. They are pivotal in the goal of stopping the development of cancer before it starts. Prevention trials are unique in that they not only have some of the same requirements and challenges as treatment trials but also have challenges that may make their design more complex. This paper aims to discuss some types of prevention trials and highlight their most common design challenges, including large sample size requirements, slow accrual rates with long accrual duration, extended follow-up periods with trial adherence issues and missing data, endpoints that require extended follow-up or have a high level of confounding, and problems with optimizing study design. This article provides real study examples and suggestions for designing prevention clinical trials while mitigating the known issues they face.

Abstract The intracluster correlation coefficient (ICC) measures the correlation of observations within clusters and is a key parameter for power and sample size calculations for cluster randomized trials (CRTs). To facilitate the design of future CRTs within the National Cancer Institute Community Oncology Research Program (NCORP), all studies from the NCORP website were reviewed to identify completed CRTs. ICCs for primary and secondary outcomes (when available) were ascertained from these trials and summarized in this article as a resource for future trial development. Although ICCs are relatively small for many outcome cluster combinations, that is not always the case, so consideration should always be given to the specific outcome of interest, trial design, and type of cluster when estimating an ICC to facilitate trial development.

Abstract Cancer care delivery research trials conducted within the National Cancer Institute (NCI) Community Oncology Research Program (NCORP) routinely implement interventions at the practice or provider level, necessitating the use of cluster randomized controlled trials (cRCTs). The intervention delivery requires cluster-level randomization instead of participant-level, affecting sample size calculation and statistical analyses to incorporate correlation between participants within a practice. Practical challenges exist in the conduct of these cRCTs due to unique trial network infrastructures, including the possibility of unequal participant accrual totals and rates and staggered study initiation by clusters, potentially with differences between randomized arms. Execution of cRCT designs can be complex, ie, if some clusters do not accrue participants, unintended cluster-level crossover occurs, how best to identify appropriate cluster-level stratification, timing of randomization, and multilevel eligibility criteria considerations. This article shares lessons learned with potential mitigation strategies from 3 NCORP cRCTs.

Abstract Patient-reported outcomes (PROs) are often collected in cancer clinical trials. Data obtained from trials with PROs are essential in evaluating participant experiences relating to symptoms, financial toxicity, or health-related quality of life. Although most features of clinical trial design, implementation, and analyses apply to trials with PROs, several considerations are unique. In this paper, we focus on specific issues such as selection of the tool, timing and frequency of assessments, and data collection methods. We discuss how the estimand framework can be used in connection with PROs, properties of common estimation methods, and handling of missing outcomes. With a plethora of literature available, we aim to summarize best practices and pragmatic approaches to the design and analysis of the studies incorporating PROs.

Objective: To assess the effect of a practice-level preoperative frailty screening and optimization toolkit (OPTI-Surg) on postoperative functional recovery and complications in elderly cancer patients undergoing major surgery. Background: Frailty is common in older adults. It increases the risk of poor postoperative functional recovery and complications. The potential for a practice-level screening/optimization intervention to improve outcomes is unknown. Methods: Thoracic, gastrointestinal, and urologic oncological surgery practices within the National Cancer Institute Community Oncology Research Program (NCORP) were randomized 1:1:1 to usual care (UC), OPTI-Surg, or OPTI-Surg with an implementation coach. OPTI-Surg consisted of the Edmonton Frail Scale and guided recommendations for referral interventions. Patients 70 years old or above undergoing curative intent surgery were eligible. The primary outcome was 8 weeks postoperative function (kcal/wk). The key secondary outcome was complications within 90 days. Mixed models were used to compare UC to the 2 OPTI-Surg arms combined. Results: From July 2019 to September 2022, 325 patients were enrolled in 29 practices. One hundred ninety-nine (64 UC, 135 OPTI-Surg) and 279 (78 UC, 201 OPTI-Surg) were evaluable for primary and secondary analysis, respectively. UC and OPTI-Surg patients did not significantly differ in total caloric expenditure (2.2 UC, 2.0 OPTI-Surg) after adjusting for baseline function (P=0.53). UC and OPTI-Surg patients did not significantly differ in postoperative complications (25.6% UC, 35.3% OPTI-Surg, P=0.5). Conclusions: Frailty assessment was successfully performed, but the OPTI-Surg intervention did not improve postoperative function nor reduce postoperative complications compared with UC. Future analysis will explore practice-level factors associated with toolkit implementation and the differences between the coaching and noncoaching arms.

Abstract Background Minimal clinically important differences (MCIDs) quantify the clinical relevance of quality of life results at the individual patient and group level. The aim of this study was to estimate the MCID for the Brief Fatigue Inventory (BFI) and the Worst and Usual Fatigue items in patients with brain or CNS cancer undergoing curative radiotherapy. Methods Data from a multi-site prospective registry was used. The MCID was calculated using distribution-based and anchor-based approaches. For the anchor-based approach, the fatigue item from the PROMIS-10 served as the anchor to determine if a patient improved, deteriorated, or had no change from baseline to end of treatment (EOT). We compared the unadjusted means on the BFI for the 3 groups to calculate the MCID. For the distribution-based approaches, we calculated the MCID as 0.5 SD of the scores and as 1.96 times the standard error of measurement. Results Three-hundred and fifty nine patients with brain or CNS tumors undergoing curative radiotherapy filled out the 9-item BFI at baseline and EOT. The MCID for the BFI was 1.33 (ranging from 0.99 to 1.70 across the approaches), 1.51 (ranging from 1.16 to 2.02) and 1.76 (ranging from 1.38 to 2.14) for the usual and worst fatigue items, respectively. Conclusions This study provides the MCID ranges for the BFI and Worst and Usual fatigue items, which will allow clinically meaningful conclusions to be drawn from BFI scores. These results can be used to select optimal treatments for patients with brain or CNS cancer or to interpret BFI scores from clinical trials.

AbstractThe role of collaborative biostatisticians and epidemiologists in academic medical centres and how their degree type, supervisor type and sex influences recognition and feelings of respect is poorly understood. We conducted a cross‐sectional survey of self‐identified biostatisticians and epidemiologists working in academic medical centres in the United States or Canada. The survey was sent to 341 contacts at 125 institutions who were asked to forward the survey invitation to faculty and staff at their institution and posted on Community sections of the American Statistical Association website. Participants were asked a variety of questions including if they felt pressured to produce specific results, whether they had intellectual and ethical freedom to pursue appropriate use of statistical methods in collaborative research and if they felt their contributions were appropriately recognized by collaborators. We received responses from 314 biostatisticians or related methodologists. A majority were female (59%), had a doctorate degree (52%) and reported to a statistician or biostatistician supervisor (69%). Overall, most participants felt valued by their collaborators, but that they did not have sufficient calendar time to meet deadlines. Doctoral‐level participants reported more autonomy in their collaborations than master's level participants. Females were less likely to feel recognized and respected compared with males. The survey results suggest that while most respondents felt valued by their collaborators, they have too many projects and need more time to critically review research. Further research is needed to understand why response differs by sex and how these responses fluctuate over time.