Participation of Patients From Racial and Ethnic Minority Groups in Phase 1 Early Cancer Drug Development Trials in the US, 2000-2018.

Importance: Despite federal initiatives encouraging the enrollment of individuals from racial and ethnic minority groups in US clinical trials, no studies to date have specifically examined demographic disparities among participants in phase 1 drug development trials for patients with metastatic cancer. Objective: To assess trends in the enrollment of patients from racial and ethnic minority groups in US phase 1 therapeutic drug trials for metastatic cancer from 2000 to 2018. Design, Setting, and Participants: In this cross-sectional study, ClinicalTrials.gov was queried in July 2021 to identify completed phase 1 drug trials for metastatic cancer in the US from January 1, 2000, to December 31, 2018, with published results, yielding 221 phase 1 trials with 8309 participants aged 18 years or older with metastatic solid tumors. Proportions of each racial and ethnic group of trial participants were compared with that from the North American Association of Central Cancer Registries' Cancer in North America (CiNA) database. Statistical analysis was performed from July 12, 2021, to March 15, 2022. Main Outcomes and Measures: For each racial and ethnic group, the difference between trial and CiNA proportions was examined using a 2-sample test for equality of proportions with continuity correction. Results: The 8309 phase 1 trial participants (4198 men [50.5%]; median age, 59 years) included 23 American Indian or Alaska Native participants (0.3%), 371 Asian or Pacific Islander participants (4.5%), 514 Black participants (6.2%), 401 of 5076 Hispanic or Latinx participants (7.9%), and 7154 White participants (86.1%). Industry funded 165 of the 221 trials (74.7%). White patients were overrepresented overall compared with the corresponding CiNA cohort (7154 of 8309 [86.1%] vs 4 113 096 of 4 891 486 [84.1%]; difference, 2.0 percentage points; P < .001). There was an increase in overrepresentation of White patients from 2000 to 2011 (trials, 2780 of 3245 [85.7%]; CiNA, 2 378 019 of 2 800 711 [84.9%]; difference, 0.8 percentage points; P = .23) to 2012-2018 (trials, 4374 of 5063 [86.4%]; CiNA, 1 735 077 of 2 090 775 [82.9%]; difference, 3.5 percentage points; P < .001) and corresponding worsening representation of American Indian or Alaska Native patients (2000-2011: trials, 10 of 3245 [0.3%]; CiNA, 10 905 of 2 800 711 [0.4%]; difference, -0.08 percentage points; 2012-2018: trials, 13 of 5063 [0.3%]; CiNA, 9484 of 2 090 775 [0.5%]; difference, -0.20 percentage points), Asian or Pacific Islander patients (2000-2011: trials, 121 of 3245 [3.7%]; CiNA, 75 033 of 2 800 711 [2.7%]; difference, 1.1 percentage points; 2012-2018: trials, 151 of 5063 [3.0%]; CiNA 70 535 of 2 090 775 [3.4%]; difference, -0.75 percentage points), Black patients (2000-2011: trials, 244 of 3245 [7.5%]; CiNA, 322 701 of 2 800 711 [11.5%]; difference, -4.0 percentage points; 2012-2018: trials, 270 of 5063 [5.3%]; CiNA, 255 625 of 2 090 775 [12.2%]; difference, -6.9 percentage points), and Hispanic or Latinx patients (2000-2011: trials, 161 of 1792 [9.0%]; CiNA, 169 297 of 2 800 711 [6.0%]; difference, 3.0 percentage points; 2012-2018: trials, 240 of 3295 [7.3%]; CiNA, 156 118 of 2 090 775 [7.5%]; difference, -0.2 percentage points). Similar disparities were observed when comparing industry-funded and academic center-sponsored trials. Conclusions and Relevance: In this cross-sectional study of participants in phase 1 clinical trials of drugs for metastatic cancer, worsening disparities were observed over time in the accrual of patients from racial and ethnic minority groups. These findings may represent widening inequalities in access to trial sites and worsening systemic biases. More efforts are needed to diversify phase 1 cancer drug trials to improve equity in access to new treatments and to ensure that safety and efficacy findings from early drug trials are generalizable across populations.

Child Disruptions, Remote Learning, and Parent Mental Health during the COVID-19 Pandemic.

New York City (NYC) was an epicenter of the COVID-19 pandemic, which resulted in broad economic, social, and emotional consequences in the lives of individuals. The current study examined associations between pandemic-related stressors and adverse mental health symptoms among NYC parents/caregivers. Community-based participatory research was used to develop a survey, and logistic regression models were utilized to assess associations between factors including disruptions in child routines and remote learning, and parent-reported symptoms of stress, anxiety, depression, and post-traumatic stress disorder (PTSD). Some 91.0% of parents reported stress and 41.2, 26.6, and 33.7% reported symptoms of anxiety, depression, and PTSD, respectively. Most parents (87.6%) reported cancellation of at least one child activity. Of the parents, 60.3% reported that their children participated in remote learning and the majority (70.3%) reported feeling overwhelmed by it. Having more cancelled child activities was associated with higher odds of reported mental health symptoms, with not being able to play outside associated with higher odds of anxiety (1.80 (1.26, 2.58), p = 0.001), depression (1.93 (1.29, 2.91), p = 0.002), PTSD (1.64 (1.13, 2.39), p = 0.009), and stress (2.34 (1.27, 4.44), p = 0.008). Feeling overwhelmed by remote learning was also associated with higher odds of all four outcomes. Pre-existing mental illness, lower resilience scores, and lower socioeconomic status emerged as additional factors associated with symptoms of mental illness. These findings highlight the importance of resources to minimize adverse psychological effects among vulnerable families.

Disparities in Care Management During Terminal Hospitalization Among Adults With Metastatic Cancer From 2010 to 2017.

Importance: Many patients with metastatic cancer receive high-cost, low-value care near the end of life. Identifying patients with a high likelihood of receiving low-value care is an important step to improve appropriate end-of-life care. Objective: To analyze patterns of care and interventions during terminal hospitalizations and examine whether care management is associated with sociodemographic status among adult patients with metastatic cancer at the end of life. Design, Setting, and Participants: This retrospective, population-based cross-sectional study used data from the Healthcare Cost and Utilization Project to analyze all-payer, encounter-level information from multiple inpatient centers in the US. All utilization and hospital charge records from national inpatient sample data sets between January 1, 2010, and December 31, 2017 (n = 58 761 097), were screened. The final cohort included 21 335 patients 18 years and older at inpatient admission who had a principal diagnosis of metastatic cancer and died during hospitalization. Data for the current study were analyzed from January 1, 2010, to December 31, 2017. Exposures: Patient demographic characteristics, patient insurance status, hospital location, and hospital teaching status. Main Outcomes and Measures: Receipt of systemic therapy (including chemotherapy and immunotherapy), receipt of invasive mechanical ventilation, emergency department (ED) admission, time from hospital admission to death, and total charges during a terminal hospitalization. Results: Among 21 335 patients with metastatic cancer who had terminal hospitalizations between 2010 and 2017, the median age was 65 years (interquartile range, 56-75 years); 54.0% of patients were female; 0.5% were American Indian, 3.3% were Asian or Pacific Islander, 14.1% were Black, 7.5% were Hispanic, 65.9% were White, and 3.1% were identified as other; 58.2% were insured by Medicare or Medicaid, and 33.2% were privately insured. Overall, 63.2% of patients were admitted from the ED, 4.6% received systemic therapy, and 19.2% received invasive mechanical ventilation during hospitalization. Racial and ethnic minority patients had a higher likelihood of being admitted from the ED (Asian or Pacific Islander patients: odds ratio [OR], 1.43 [95% CI, 1.20-1.72]; P < .001; Black patients: OR, 1.39 [95% CI, 1.27-1.52]; P < .001; and Hispanic patients: OR, 1.45 [95% CI, 1.28-1.64]; P < .001), receiving invasive mechanical ventilation (Black patients: OR, 1.59 [95% CI, 1.44-1.75]; P < .001), and incurring higher total charges (Asian or Pacific Islander patients: OR, 1.35 [95% CI, 1.13-1.60]; P = .001; Black patients: OR, 1.23 [95% CI, 1.13-1.34]; P < .001; and Hispanic patients: OR, 1.50 [95% CI, 1.34-1.69]; P < .001) compared with White patients. Privately insured patients had a lower likelihood of being admitted from the ED (OR, 0.47 [95% CI, 0.44-0.51]; P < .001), receiving invasive mechanical ventilation (OR, 0.75 [95% CI, 0.69-0.82]; P < .001), and incurring higher total charges (OR, 0.64 [95% CI, 0.59-0.68]; P < .001) compared with Medicare and Medicaid beneficiaries. Conclusions and Relevance: In this study, patients with metastatic cancer from racial and ethnic minority groups and those with Medicare or Medicaid coverage were more likely to receive low-value, aggressive interventions at the end of life. Further studies are needed to evaluate the underlying factors associated with disparities at the end of life to implement prospective interventions.

The ability of the kinesin-2 heterodimer KIF3AC to navigate microtubule networks is provided by the KIF3A motor domain.

Heterodimeric kinesin family member KIF3AC is a mammalian kinesin-2 that is highly expressed in the central nervous system and has been implicated in intracellular transport. KIF3AC is unusual in that the motility characteristics of KIF3C when expressed as a homodimer are exceeding slow, whereas homodimeric KIF3AA, as well as KIF3AC, have much faster ATPase kinetics and single molecule velocities. Heterodimeric KIF3AC and homodimeric KIF3AA and KIF3CC are processive, although the run length of KIF3AC exceeds that of KIF3AA and KIF3CC. KIF3C is of particular interest because it exhibits a signature 25-residue insert of glycine and serine residues in loop L11 of its motor domain, and this insert is not present in any other kinesin, suggesting that it confers specific properties to mammalian heterodimeric KIF3AC. To gain a better understanding of the mechanochemical potential of KIF3AC, we pursued a single molecule study to characterize the navigation ability of KIF3AC, KIF3AA, and KIF3CC when encountering microtubule intersections. The results show that all three motors exhibited a preference to remain on the same microtubule when approaching an intersection from the top microtubule, and the majority of track switches occurred from the bottom microtubule onto the top microtubule. Heterodimeric KIF3AC and homodimeric KIF3AA displayed a similar likelihood of switching tracks (36.1 and 32.3%, respectively). In contrast, KIF3CC detached at intersections (67.7%) rather than switch tracks. These results indicate that it is the properties of KIF3A that contribute largely to the ability of KIF3AC to switch microtubule tracks to navigate intersections.