Participation In Randomized Clinical Trials Research Articles

Five-year follow-up of randomized clinical trial for pre-emptive inferior mesenteric artery embolization during endovascular aneurysm repair

Type II endoleak (T2EL) is the most common type of endoleak after endovascular aneurysm repair (EVAR) and a common indication for reintervention due to late sac enlargement. Although pre-emptive embolization of the inferior mesenteric artery (IMA) has been proposed to prevent this, no studies have prospectively demonstrated its efficacy. This study aimed to prove the validity of IMA embolization during EVAR in selective cases by analyzing the mid-term outcomes of a randomized clinical trial (RCT). This single-center, parallel-group, non-blinded RCT included participants at high risk of T2EL, characterized by a patent IMA in conjunction with one or more following risk factors: a patent IMA ≥3 mm in diameter, lumbar arteries ≥2 mm in diameter, or an aortoiliac-type aneurysm. The participants were randomly assigned to two groups in a 1:1 ratio: one undergoing EVAR with IMA embolization and the other without. The primary endpoint was T2EL occurrence. The secondary endpoints included aneurysm sac changes and reintervention. In addition to RCT participants, outcomes of patients with low-risk of T2EL were also analyzed. The embolization and non-embolization groups each contained 53 patients. Five-year follow-up after the last patient enrolment revealed that T2ELs occurred in 28.3% and 54.7% of patients in the IMA embolization and non-embolization groups, respectively (P=.006). Both freedom from T2EL-related sac enlargement ≥5 mm and cumulative incidence of sac shrinkage ≥5 mm were significantly higher in the IMA embolization group than in the non-embolization group (95.5% vs. 73.6% at 5 years; P=.021, 54.2% vs. 33.6% at 5 years; P=.039). The freedom from T2EL-related sac enlargement ≥10 mm, an alternative indicator for T2EL-related reintervention, showed similar results (100% vs. 90.4% at 5 years; P=.019). Outcomes in the low-risk group were preferable than those in the non-embolization group and comparable to those in the IMA embolization group. A lower threshold for pre-emptive IMA embolization when implementing EVAR would be more appropriate if limited to patients at high risk of T2ELs.

A randomized clinical trial to support adherence regimens in children with epilepsy: Examining potential mechanisms of change

ObjectiveA family-tailored education and problem-solving intervention, Supporting Treatment Adherence Regimens (STAR), was developed to address the adherence challenges common in youth with epilepsy and their families. Randomized clinical trial (RCT) results indicated a 21% adherence improvement in the STAR group compared with an education-only (EO) group 12-months post-intervention. The current study examined group differences (STAR vs. EO) in epilepsy-specific knowledge, barriers to medication adherence, problem-solving skills, caregiver emotional distress, and family functioning over time and whether these factors mediated group differences in adherence at 12-months post-intervention. MethodsTwo-hundred children (ages 2–12) with epilepsy and their caregivers were included as RCT participants. Children with new-onset epilepsy and adherence <95% were randomized to receive either the STAR (n = 27) or EO (n = 29) intervention. Caregivers completed questionnaires assessing outcomes of interest at baseline, midpoint of the intervention, post-intervention, and 3-, 6-, and 12-month follow-ups. Regression-based analyses of covariance and longitudinal mixed effect linear models were conducted. ResultsResults generally revealed no significant group differences across outcomes of interest at post-intervention or over time. However, one significant model did emerge for social problem-solving skills (b = −1.74, p = 0.04), such that these scores were initially higher in the STAR group compared to the EO group, then decreased slightly in the STAR group over time while remaining stable in the EO group. None of these factors mediated group differences in adherence at 12-months post-intervention. ConclusionFuture research should examine other potential mechanisms of treatment change after adherence interventions, such as STAR. Nonsignificant findings can inform the development of future study designs and intervention efforts.

Disparities between randomized clinical trial participants and sepsis patients in real-world

BackgroundThe external validity or “generalizability” of randomized controlled trials (RCTs) often needs be considered when making treatment decisions. We evaluate whether participants in large multicenter RCTs investigating sepsis were similar in age, disease severity, comorbidities, and mortality to the general population of sepsis patients. MethodsUsing MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials, RCTs that enrolled 100 or more adult sepsis patients from two or more sites published from 01 January 2000 to 04 August 2019 were identified. The weighted mean age of trial participants was calculated as the main variable, and it was compared with the mean ages of the overall populations derived from the MIMIC database and the EICU database. Two researchers independently screened all abstracts and performed data extraction, then aggregated the data using a random effects model. Multiple linear regression was used to determine whether any factors were significantly associated with age disparities. ResultsThe mean age of the 60,577 participants in the 94 trials included in the analysis was significantly lower than those of the patients in the MIMIC and EICU databases (weighted mean age 62.28 years vs. 64.47 years for MIMIC and 65.20 years for EICU; both p < 0.001). Trial participants were less likely to have known comorbidities such as diabetes (13.96% vs. 30.64% for MIMIC and 35.75% for EICU; both p < 0.001). The weighted mortality rate in trial participants was higher than that in patients in the MIMIC and EICU databases (29.33% vs. 20.72% for MIMIC and 17.53% for EICU; both p < 0.001). Differences in age, severity score, and comorbidities remained statistically significant in sensitivity analyses. Multivariable regression suggested that commercially supported trials were more likely to include patients with higher severity scores (p = 0.002), but after adjustment for study region and sepsis diagnosis inclusion in such trials was not significantly associated with age. ConclusionsOn average, trial participants were younger than the general sepsis patient population. Commercial support influenced patient selection. Efforts to understand and address the above-described patient disparities are necessary to improve the generalizability of RCT results.Trial registration:PROSPERO CRD42019145692.

Patient-reported usefulness of an intervention to promote job retention among women undergoing (neo)adjuvant breast cancer chemotherapy.

1586 Background: Women who undergo (neo)adjuvant breast cancer chemotx are at risk of job loss, especially if they lack work accommodations. We developed TEAMWork (Talking to Employers And Medical staff about Work), an English/Spanish mobile application (app) to help women identify work accommodations relevant to their needs, negotiate with their employers to receive these accommodations, and communicate with the clinic team to manage symptoms. TEAMWork will be compared to a booklet as a job-retention tool in an ongoing randomized clinical trial (RCT). Here we present acceptability data based on RCT participants’ perceptions of the app’s usefulness. Methods: Eligible participants were women aged 18-64, who spoke English/Spanish, were able to use and had access to a smartphone/tablet, were undergoing or planned to undergo (neo)adjuvant chemotx for stage I-III breast cancer, and were working full or part time for pay. Women who had stopped working due to the diagnosis were eligible. Those who had stopped working for reasons unrelated to breast cancer (e.g., prior illness disability) were ineligible. Online surveys were self-administered or administered interview-style (per participant preference) at baseline and midway through the planned chemotx. In the second survey, participants were asked if they had used TEAMWork at all since enrollment; those who said they had used it were asked about the app’s usefulness. Results: 58 participants received the app; 56 received the booklet. 64% were white, 18% were Black, and 12% were Asian; 7% were Hispanic. 4% were Spanish-speaking. 79% had at least a college education. When surveyed half-way through their chemotx regimen, 62% of those randomized to the app said they had used the app; only 25% of those randomized to the booklet said they had used the booklet (p&lt;0.0001). Among those who reported having used the app (n=36), 86% said they were very (44%) or somewhat (42%) satisfied with TEAMWork, and 94% said they thought TEAMWork would be very (61%) or somewhat (33%) helpful to other patients. Additional details about the perceived usefulness of the app are shown. Conclusions: Compared to participants randomized to the booklet, more than twice as many who received the app reported that they had used their assigned intervention. Among those who used it, the app was well-received and was deemed especially helpful for communicating with medical providers. Recruitment to the RCT is ongoing, and job retention results will be presented when data are mature. Efforts are under way to increase the diversity of the study sample based on ethnicity, language, and education. Clinical trial information: NCT03572374 .[Table: see text]

Representation of age, race and ethnicity in real-world evidence (RWE), randomized clinical trial (RCT), and Surveillance, Epidemiology, and End Results (SEER) cancer patient registry data in advanced renal cell carcinoma (aRCC).

e18672 Background: Representation of key demographic characteristics in real-world settings and clinical trial environments is medically necessary to address evidentiary gaps and disparities in clinical outcomes among patients with advanced renal cell carcinoma (aRCC). We characterized age, race, and ethnicity in patients with aRCC in real-world evidence (RWE), corresponding randomized controlled trials (RCTs), and Surveillance, Epidemiology, and End Results (SEER) data during contemporaneous periods spanning 2017-2022. Methods: Demographic characteristics were assessed from one RWE chart review study, two RCTs (Checkmate 214 and Keynote 426), and a SEER cohort based on RCT/RWE eligibility criteria and compared across data sources using 2-sided chi-square or t-tests. Results: Age, race and ethnicity were collected for 4,821 patients (RWE: n = 635, 13.2%; RCT: Checkmate 214 n = 1,096 and Keynote 426 n = 861, 40.6% across both RCTs; SEER: n = 2,229, 46.2%). RCT participants were younger at metastatic diagnosis (60.9 vs 65.1 years) and at 1L therapy initiation (60.9 vs 65.7 years) compared to patients in RWE and SEER, respectively (both p &lt; 0.0001). Black patients accounted for 17.2% in RWE, 1.6% in RCT, and 4.8% in SEER data, and Asian patients accounted for 6.3% in RWE, 11.8% in RCT, and 6.0% in SEER data. Hispanic representation was significantly higher in RWE studies than RCT studies, (15.0% vs 3.4%), P&lt; .001. A significantly greater proportion of white patients was observed in RCTs than RWE (84.5% vs 71.7%) and greater representation of non-Hispanic white patients was observed in SEER vs RWE (67.5% vs 60.3%), P&lt; .001 (Table 1). Conclusions: This study describes existing disparities in representation of age, race, and ethnicity among patients with aRCC in research. RCTs had lower representation of older, Black, and Hispanic patients with aRCC compared to SEER and RWE studies. Despite limitations including sparse data available among Hispanics in RCTs, RWE studies can provide greater visibility to traditionally medically underrepresented patients with aRCC. [Table: see text]

Health-related quality of life among transthyretin amyloid cardiomyopathy patients.

Transthyretin amyloid cardiomyopathy (ATTR CM) is a progressive and severe heart disease with physical and psychological implications. The Nordic PROACT study was conducted to investigate the health-related quality of life (HRQoL) in ATTR CM patients. The Nordic PROACT study was a cross-sectional non-interventional study conducted in 12 cardiology hospital clinics across Norway, Sweden, Finland and Denmark. Men and women aged ≥18years diagnosed with symptomatic ATTR CM were included. The investigator provided information on medical history, biomarkers, current treatment, co-morbidities and disease severity according to the New York Heart Association (NYHA) class and the National Amyloidosis Centre (NAC) staging. Patients completed the HRQoL questionnaires in the form of the Kansas City Cardiomyopathy Questionnaire (KCCQ), the EQ-5D-5L index with Visual Analog Scale (VAS), and the Major Depression Inventory (MDI). A total of 169 patients (mean ± SD age 77.7±6.2years) were included. Ninety-two per cent were men. Seventy-six per cent had wildtype ATTR CM (ATTRwt CM) and 15% had a hereditary form of ATTR CM (ATTRv CM) while 9% were genetically unclassified. Most patients were in NYHA class II (54%) and NAC stage 1 (53%). Participation in randomized clinical trials (RCT) was noted in 58% of the patients. The 169 ATTR CM patients had a mean±SD KCCQ score of 64.3±23.1 for total symptom score, 64.8±20.9 for overall summary score (OSS) and 65.1±21.5 for clinical summary score. The EQ-5D-5L total utility score was 0.8±0.2 and the EQ-5D-5L VAS score was 62.9±20.6. The vast majority (89%) did not report any signs of depression. Patients with ATTRv CM had a higher KCCQ OSS as compared with ATTRwt CM, while EQ-5D-5L utility score, EQ-5D-5L VAS and MDI were similar. Non-RCT participants had a poorer HRQoL as compared with RCT participants as reflected in lower KCCQ OSS and EQ-5D-5L VAS scores and a higher MDI score. Patients with higher NYHA classes and NAC disease stages had a poorer HRQoL as demonstrated by lower KCCQ and EQ-5D-5L scores and higher MDI scores. Correlation between KCCQ, EQ-5D-5L and MDI and the covariate NYHA class remained significant (P<0.05) after adjusting for multiple testing. KCCQ scores were lower than previously reported for patients with other heart diseases of non-ATTR CM origin. The HRQoL measures correlated well to NYHA class and NAC disease stage. The prevalence of depression appeared to be low.

Women in cardiology leadership of randomized clinical trials and participation of women in late-breaking clinical trials: has the COVID-19 pandemic changed a thing or not exactly?

Abstract Introduction Despite considerable developments made in the representation of women in cardiology (WIC) recently, there still remain substantial disparities in the representation of women participants in clinical trials, as well as women physicians and scientists in clinical trial leadership. Under-representation of women in Randomized Clinical Trials (RCTs) remains the bane of the modern medicine, impeding the development of sex-specific guidelines in cardiovascular diseases. Female leadership in clinical trials has been shown to enhance the inclusion of women as trial participants. Furthermore, while the COVID-19 pandemic has impacted women in academia, there is no data thus far reporting the impact of the pandemic in terms of presenters and leadership of late-breaking clinical trials (LBCT) in cardiology during this period. Purpose We aimed to determine inclusion of WIC in LBCTs leadership and their correlation to inclusion of women in reported RCTs. Methods In our comprehensive analysis, we included all LBCTs presented at major international cardiovascular meetings reported over the period of January 2020 to February 2022. Data were derived from the original presentation at the meeting and/or simultaneous/ subsequent publication of manuscript. Sex of the presenter (woman or man), was assessed by either original videos of the presentation at the meeting, or based on pronoun use in the biographies derived from institutional profiles. The presence or absence of reporting of sex distribution of study participants were also recorded from original presentation at the meeting and/or published manuscript. Proportion of women included in each trial was sourced from either original publication or calculated from any similar data shown during the presentations. Results A total of 400 of RCTs from 19 meetings were included with a total of 400 presenters/principal investigators recorded – 32 (8%) women and 368 (92%) men. There were no significant differences between 2020 and 2021 [15 (7.2%) women in 2021 vs. 17 (19.3%) in 2020 (P=0.446)]. Proportions of women included in RCTs with WIC (37.3%) vs. non-WIC (38.7%) presenters were comparable (p=0.559), while 45% of RCTs didn't report sex distribution of participants. Except for 2 meetings (CRT 2020 and 2022), all others were virtual. Conclusion WIC representation as RCTs presenters was significantly low, despite the opportunity of virtual attendance afforded during the COVID-19 pandemic. Modest inclusion of women irrespective of sex of RCT leadership emphasizes multi-level problems that require more actionable solutions: i.e. implicit bias training started as early as medical school, continuing education on necessity for diversity, equity and inclusion, patient and public involvement, and comprehensive guidance on trial design, such that future RCT participants reflect the populations intended to treat. Funding Acknowledgement Type of funding sources: None.

Unrelated Cord Blood Transplantation in Children, Adolescents, and Young Adults with Acute Leukemia or Myelodysplastic Syndrome: A Retrospective Comparative Study from the French Society for Bone Marrow Transplantation and Cellular Therapy Between Real-World Data and Previously Reported Results of a Randomized Clinical Trial

We previously reported results of a French randomized clinical trial (RCT) comparing the risk of transplantation failure (including transplant-related mortality [TRM], engraftment failure, and autologous recovery) in single and double unrelated cord blood (UCB) transplantation in children and young adults with hematologic malignancies. We concluded that single-UCB transplantation with an adequate cell dose is the standard of care, leading to a 70% two-year overall survival (OS). It remains unclear, however, whether RCT participants have better outcomes than comparable patients not treated in the setting of a clinical trial. We compared the characteristics and outcomes of RCT participants (n=137) to a Francophone population-based registry of patients (real-world [RW] group) fulfilling the eligibility criteria used in our RCT and transplanted with 1 or 2 UCB units after a myeloablative conditioning (MAC) regimen between March 2015 (end of inclusion in the RCT) and February 2019 (n=141). The primary endpoint was the 2-year cumulative incidence (CI) of transplantation strategy failure as defined in our RCT. The 2 groups were comparable in terms of age, disease distribution, hematologic status at transplantation, follow-up, and HLA compatibility. Patients in the RW group were more likely to be transplanted with a single-unit UCB (87.9% versus 49.6%, P< .001) and to receive a radiation-free regimen (39.0% versus 60.6%, P< .001). The 2-year CI of transplantation strategy failure, TRM, and the 2-year probability of OS were similar between the 2 groups, although the relapse risk was higher in the RW group (31.2% ± 7.7% versus 20.4% ± 6.8%, P= .01), resulting in a significantly lower disease-free survival (DFS) (59.2% ± 8.4% versus 69.3% ± 8.0%, P= .047). This difference remained statistically significant only in the group of patients with acute lymphoid leukemia (ALL) who did not receive the conditioning regimen recommended by the RCT (fludarabine 75 mg/m2, total body irradiation 12 Gy, cyclophosphamide 120 mg/kg). The results of our RCT appear to be reproducible in real-world conditions, provided that the same cord blood selection criteria and conditioning regimen are used.

Participation of Lower and Upper Middle–Income Countries in Clinical Trials Led by High-Income Countries

Many randomized clinical trials (RCTs) led by high-income countries (HICs) now enroll patients from lower middle-income countries (LMICs) and upper middle-income countries (UMICs). Although enrolling diverse populations promotes research collaborations, there are issues regarding which countries participate in RCTs and how this participation may contribute to global research. To describe which UMICs and LMICs participate in RCTs led by HICs. A cross-sectional study of all oncology RCTs published globally during January 1, 2014, to December 31, 2017, was conducted. The study cohort was restricted to RCTs led by HICs that enrolled participants from LMICs and UMICs. Study analyses were conducted in November 1, 2021, to May 31, 2022. A bibliometric approach (Web of Science 2007-2017) was used to explore whether RCT participation was proportional to other measures of cancer research activity. Participation in RCTs (ie, percentage of RCTs in the cohort in which each LMIC and UMIC participated) was compared with country-level cancer research bibliometric output (ie, percentage of total cancer research bibliometric output from the same group of countries that came from a specific LMIC and UMIC). Among the 636 HIC-led RCTs, 186 trials (29%) enrolled patients in LMICs (n = 84 trials involving 11 LMICs) and/or UMICs (n = 181 trials involving 26 UMICs). The most common participating LMICs were India (42 [50%]), Ukraine (39 [46%]), Philippines (23 [27%]), and Egypt (12 [14%]). The most common participating UMICs were Russia (115 [64%]), Brazil (94 [52%]), Romania (62 [34%]), China (56 [31%]), Mexico (56 [31%]), and South Africa (54 [30%]). Several LMICs are overrepresented in the cohort of RCTs based on proportional cancer research bibliometric output: Ukraine (46% of RCTs but 2% of cancer research bibliometric output), Philippines (27% RCTs, 1% output), and Georgia (8% RCTs, 0.2% output). Overrepresented UMICs include Russia (64% RCTs, 2% output), Romania (34% RCTs, 2% output), Mexico (31% RCTs, 2% output), and South Africa (30% RCTs, 1% output). In this cross-sectional study, a substantial proportion of RCTs led by HICs enrolled patients in LMICs and UMICs. The LMICs and UMICs that participated in these trials did not match overall cancer bibliometric output as a surrogate for research ecosystem maturity. Reasons for this apparent discordance and how these data may inform future capacity-strengthening activities require further study.

Monitoring COVID-19 vaccine use in Italian long term care centers: The GeroCovid VAX study

The COVID-19 pandemic has changed routine care practice for older persons, especially in those with frailty living in long term care (LTC) facilities. Due to the high mortality rates of Nursing home (NH) residents during the first wave of the COVID-19 pandemic, priority for COVID-19 vaccinations was given to this vulnerable population. However, the safety and efficacy of such vaccines in older frail elders remains questionable due to the fact that initial randomized clinical trials (RCTs) for such vaccines did not include this population. This type of discrimination in patient participation in RCTs continues and has been recognized in the literature. Nevertheless, in the context of a worldwide emergency, COVID-19 vaccination in older persons living in LTC facilities may provide a solid basis to protect against negative outcomes, such as COVID-19 infection and death. In this report, we present the protocol of the GeroCovid Vax study, an Italian study that began in February 2021 which is aimed at investigating the safety and efficacy of the anti-SARS-CoV-2 vaccinations in older persons living in LTCs. This protocol specially aims to continuously and closely monitor events related to- and following- the anti-SARS-CoV-2 vaccination in elderly living in LTC facilities. In this report, we will provide information related to the study protocol and describe baseline characteristics of the sample.

Representation and Outcomes of Individuals With Schizophrenia Seen in Everyday Practice Who Are Ineligible for Randomized Clinical Trials

Most evidence about efficacy and safety of antipsychotics in schizophrenia spectrum disorders relies on randomized clinical trials (RCTs). However, owing to their strict eligibility criteria, RCTs represent only a part of the real-world population (ie, unselected patients seen in everyday clinical practice), which may result in an efficacy-effectiveness gap. To quantify the proportion of real-world individuals with schizophrenia spectrum disorders who would be ineligible for participation in RCTs, and to explore whether clinical outcomes differ between eligible and ineligible individuals. This study applied eligibility criteria typically used in RCTs for relapse prevention in schizophrenia spectrum disorders to real-world populations. Individuals with diagnoses of schizophrenia spectrum disorders recorded in national patient registries in Finland and Sweden were identified. Individuals who had used antipsychotics continuously for 12 weeks in outpatient care were selected. Individuals were followed up for up to 1 year while they were receiving maintenance treatment with any second-generation antipsychotic (excluding clozapine). Follow-up was censored at treatment discontinuation, initiation of add-on antipsychotics, death, and end of database linkage. Proportions of RCT-ineligible individuals with schizophrenia spectrum disorders owing to any and specific RCT exclusion criteria. The risk of hospitalization due to psychosis within 1-year follow-up in ineligible vs eligible persons were compared using hazard ratios (HR) and corresponding 95% CIs. The mean (SD) age in the Finnish cohort (n = 17 801) was 47.5 (13.8) years and 8972 (50.4%) were women; the mean (SD) age in the Swedish cohort (n = 7458) was 44.8 (12.5) years and 3344 (44.8%) were women. A total of 20 060 individuals (79%) with schizophrenia spectrum disorders would be ineligible for RCTs (Finnish cohort: 14 221 of 17 801 [79.9%]; Swedish cohort: 5839 of 7458 [78.3%]). Most frequent reasons for ineligibility were serious somatic comorbidities and concomitant antidepressant/mood stabilizer use. Risks of hospitalization due to psychosis was higher among ineligible than eligible individuals (Finnish cohort: 18.4% vs 17.2%; HR, 1.14 [95% CI, 1.04-1.24]; Swedish cohort: 20.1% vs 14.8%; HR, 1.47 [95% CI, 1.28-1.92]). The largest risks of hospitalization due to psychosis were observed in individuals ineligible owing to treatment resistance, tardive dyskinesia, and history of suicide attempts. Finally, with more ineligibility criteria met, larger risks of hospitalization due to psychosis were observed in both countries. RCTs may represent only about a fifth of real-world individuals with schizophrenia spectrum disorders. Underrepresented (ineligible) patients with schizophrenia spectrum disorders have moderately higher risks of admission due to psychosis while receiving maintenance treatment than RCT-eligible patients. These findings set the stage for future studies targeting real-world populations currently not represented by RCTs.

Are Pivotal Trials for Drugs Approved for Leukemia, Myelodysplastic Syndromes, and Multiple Myeloma Representative of the Population Demographics Affected By These Diseases?

Background: There are significant disparities in cancer care and outcomes. Many new drugs have been recently approved for hematologic malignancies through randomized clinical trials (RCTs). Equitable population participation in RCTs is important to ensure proper representation of the populations suffering from the malignancies being targeted. It is uncertain whether patients enrolled in clinical trials represent the demographics of a given malignancy. In this study, we evaluate the extent to which trials match disease burden and how trial methods and results differ across racial/ethnicity/minority disparities in participation of clinical trials.Methods: We performed a retrospective review of RCTs published from 2017 to May 2021 that led to Food and Drug Administration (FDA) approval of hematological malignancy drugs (Leukemias, Multiple Myeloma (MM), Myelodysplastic Syndrome (MDS), and Myeloproliferative Neoplasm (MPN)). We excluded drugs approved for Amyloidosis, pediatric studies, Blastic Plasmacytoid Dendritic Cell Neoplasm, and Erdheim-Chester Disease (Non-Langerhans Histiocytosis). The drugs investigated were selected using FDA Databases, ‘Oncology (Cancer) / Hematologic Malignancies Approval Notifications’ and ‘Novel Drug Approvals’. A Pubmed search was conducted using the drug name and/or clinical trial number as key terms to identify manuscripts related to the approved drugs. The manuscripts were verified with respective FDA drug approval announcement to ensure that this was the appropriate study. 34 drugs were found using the inclusion/exclusion criteria, only 12 drugs had primary manuscripts with demographics including race. Data was then extracted from NIH Surveillance, Epidemiology, and End Results Program (SEER) for prevalence on 1/2018 by race for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), MM, chronic myeloid leukemia (CML), and MDS that the 12 drugs were approved for. SEER data is collected over 13 US locations.Results: The study characteristics for the 12 drugs and demographics are found in Table 1. These included 4 drugs approved for MM, 3 for AML, 2 for ALL, and one each for CML, MDS, and hairy cell leukemia with a total of 3839 patients. The study with the largest sample included 176 sites in 14 countries, and the smallest 15 sites in 2 countries. MM studies enrolled 1757 patients, with 123 (7%) Asian/Pacific Islander patients, 50 (2.8%) Black/African American, 1452 (82.6%) Whites (including Hispanics), 1(<0.1%) Native American patient, and 131 (7.4%) did not report. AML studies enrolled 812, with 112 (13.8) were Asian/Pacific Islander, 35 (4.3%) Black/African American, 616 (75.9%) Whites (including Hispanics), and 49 (6.0%) did not report. ALL studies enrolled 623, with 62 (10%) Asian/Pacific Islander, 11(1.8%) Black/African American, 495 (79.5%) Whites (including Hispanics), and 55 (8.8%) did not report. The one MDS study enrolled 80, with 0 Asian/Pacific Islander, 2 (2.5%) Black/African American, 74 (92.5%) Whites (including Hispanics), and 4 (5.0%) did not report. The one CML study enrolled 487, with 60 (12.32%) Asian/Pacific Islander, 20 (4.11%) Black/African American, 377 (77.41%) Whites (including Hispanics), and 30 (6.16%) did not report. The one hairy cell leukemia enrolled 80: with 1 (1.3%) Asian/Pacific Islander, 1 (1.3%) Black/African American, 70 (87.5%) Whites (including Hispanics), and 8 (10%) did not report. Two studies reported ethnicity, Hispanics and Non-Hispanics. Sex was not differentiated by race in the studies. All but one study showed sex overall, with 1648 Women and 2148 Men across the 12 studies. Figure 1. shows in all diseases that Black/African-Americans are underrepresented. African Americans had an 86.5% (MM), 68.% (AML), 75.8% (ALL), and 64.2% (CML) percent lower representation compared to SEER demographics. In contrast, Asian/Pacific Islanders had a percent increase from the SEER population by 58.6% (MM), 75.3% (AML), 52.1% (ALL), and 68.3% (CML). There were significant differences in all racial categories for the four disease with the exception of Native American representation in AML and CML, and White representation in ALL and CML when compared using Z-statistics.Conclusion: The misrepresentation of minorities in pivotal clinical trials may lead to results that may not fully translate to such populations. These disparities in enrollment should be corrected in future studies. [Display omitted] DisclosuresCortes: Novartis: Consultancy, Research Funding; Sun Pharma: Consultancy, Research Funding; Bristol Myers Squibb, Daiichi Sankyo, Jazz Pharmaceuticals, Astellas, Novartis, Pfizer, Takeda, BioPath Holdings, Incyte: Consultancy, Research Funding; Bio-Path Holdings, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding.

Motivation to participate and experiences of the informed consent process for randomized clinical trials in emergency obstetric care in Uganda

BackgroundInformed consent, whose goal is to assure that participants enter research voluntarily after disclosure of potential risks and benefits, may be impossible or impractical in emergency research. In low resource settings, there is limited information on the experiences of the informed consent process for randomized clinical trials in the emergency care context. The objective of this study was to explore the experiences of the informed consent process and factors that motivated participation in two obstetrics and newborn care randomized clinical trials (RCTs).MethodsThis was a qualitative study conducted among former participants of RCTs in the emergency obstetric care context, conducted at Kawempe National Referral Hospital, Uganda. It employed 30 in-depth interviews conducted from June 1, 2019 to August 30, 2019. Issues explored included attitudes about research, the purpose of the research in which they participated, motivations to take part in the study, factors that influenced enrolment decisions, and experiences of the informed consent process.ResultsRespondents felt that research was necessary to investigate the cause, prevention or complications of illness. The decisions to participate were influenced by hope for material or therapeutic benefit, trust in the healthcare system and influence of friends and family members. Many were satisfied with the informed consent process, though they did not understand some aspects of the research.ConclusionRespondents valued participation in RCTs in emergency obstetric and newborn care. Hope for benefit, altruism, desire to further scientific knowledge and trust in the investigators featured prominently in the motivation to participate. Both intrinsic and extrinsic factors were motivators for RCT participation.

Variation in Clinical Trial Results for Asthma by Environmental and Socioeconomic Exposures

Randomized clinical trials (RCTs) are generally considered the gold standard in medical research; by randomizing participants to treatment and control arms, they maximize internal validity and reduce between-group biases. RCTs, however, do not routinely examine variation by environmental and social exposures (e.g., socioeconomic status), which may impact clinical outcomes, treatment response, and study generalizability. To assess whether variation in socioeconomic positon (SEP) and environmental exposures modify treatment response, we have developed and applied Geographic Information Systems (GIS)-based methods to examine three RCTs performed by the NIH AsthmaNet network, which recruited and implemented RCTs using the same protocols across 17 U.S. cities. In preliminary analyses, we have found that: (1) compared to race-specific U.S. averages, AsthmaNet participants disproportionately live in impoverished census tracts. (2) At baseline, traffic density and SEP predicted variation in lung function, in the hypothesized directions. (3) In one longitudinal trial, we found that near-residence roadway density explained greater variation in asthma symptoms than did corticosteroid use, and that children in higher-poverty areas had significantly shorter times to first corticosteroid use. For this trial, we examined effect modification by near-residence roadway traffic and noise exposures, neighborhood violence, and health care access. Preliminary results suggest - only among higher-SES children - significantly greater negative impacts (shorter times to prednisone use) among participants receiving higher inhaled corticosteroid (ICS) doses (220 ug), relative to those receiving lower ICS doses (44 ug).Results suggest that participants in clinical trials may not be representative of U.S. asthmatics, and participants from different SES backgrounds may differentially respond to intensive corticosteroid interventions. Using spatial analysis and GIS to understand the neighborhoods of RCT participants – better accounting for socioeconomic and environmental conditions – may improve the interpretability and applicability of RCT results, by more clearly identifying subpopulations for whom a given intervention may be most effective.

Neural Connectivity Changes Facilitated by Familiar Auditory Sensory Training in Disordered Consciousness: A TBI Pilot Study.

For people with disordered consciousness (DoC) after traumatic brain injury (TBI), relationships between treatment-induced changes in neural connectivity and neurobehavioral recovery have not been explored. To begin building a body of evidence regarding the unique contributions of treatments to changes in neural network connectivity relative to neurobehavioral recovery, we conducted a pilot study to identify relationships meriting additional examination in future research. To address this objective, we examined previously unpublished neural connectivity data derived from a randomized clinical trial (RCT). We leveraged these data because treatment efficacy, in the RCT, was based on a comparison of a placebo control with a specific intervention, the familiar auditory sensory training (FAST) intervention, consisting of autobiographical auditory-linguistic stimuli. We selected a subgroup of RCT participants with high-quality imaging data (FAST n = 4 and placebo n = 4) to examine treatment-related changes in brain network connectivity and how and if these changes relate to neurobehavioral recovery. To discover promising relationships among the FAST intervention, changes in neural connectivity, and neurobehavioral recovery, we examined 26 brain regions and 19 white matter tracts associated with default mode, salience, attention, and language networks, as well as three neurobehavioral measures. Of the relationships discovered, the systematic filtering process yielded evidence supporting further investigation of the relationship among the FAST intervention, connectivity of the left inferior longitudinal fasciculus, and auditory-language skills. Evidence also suggests that future mechanistic research should focus on examining the possibility that the FAST supports connectivity changes by facilitating redistribution of brain resources. For a patient population with limited treatment options, the reported findings suggest that a simple, yet targeted, passive sensory stimulation treatment may have altered functional and structural connectivity. If replicated in future research, then these findings provide the foundation for characterizing the unique contributions of the FAST intervention and could inform development of new treatment strategies. For persons with severely damaged brain networks, this report represents a first step toward advancing understanding of the unique contributions of treatments to changing brain network connectivity and how these changes relate to neurobehavioral recovery for persons with DoC after TBI.Clinical Trial Registry: NCT00557076, The Efficacy of Familiar Voice Stimulation During Coma Recovery (http://www.clinicaltrials.gov).

Differences Between Randomized Clinical Trial Participants and Real-World Empagliflozin Users and the Changes in Their Glycated Hemoglobin Levels

Use of the sodium-glucose cotransporter 2 inhibitor empagliflozin has increased substantially since 2015. Little is known about characteristics of real-world patients who use empagliflozin or about empagliflozin's effectiveness in reducing glycated hemoglobin (HbA1c) levels in routine clinical care. To characterize real-world initiators of empagliflozin, to examine the proportion of initiators who would have been eligible for participation in phase 3 randomized clinical trials (RCTs) of empagliflozin, and to assess changes in HbA1c levels after empagliflozin initiation. This cross-sectional study used linked population-based medical databases containing complete information on redeemed prescriptions, laboratory tests, and diagnoses for all residents in Northern Denmark. A total of 7034 residents of Denmark who filled a first-time empagliflozin prescription from January 2014 to December 2018 were included. Data analysis was performed in August 2019. Empagliflozin initiation. Proportion of real-world users ineligible for RCT inclusion and absolute reduction in HbA1c level 6 months after empagliflozin initiation. Of 7034 first-time empagliflozin initiators (median [interquartile range] age, 61.50 [53.30-69.38] years; 4475 [63.6%] men), 3878 (55.1%) would have been ineligible for phase 3 RCT participation; frequent reasons were concurrent use of specific glucose-lowering drugs (1955 initiators [27.8%]), baseline HbA1c level outside the eligibility range (1772 [25.2%]), or presence of comorbidities (1067 initiators [15.3%]). Initiation of empagliflozin was associated with a mean HbA1c reduction of -0.91% (95% CI, -0.94% to -0.87%) after 6 months, similar to phase 3 RCT results. Real-world empagliflozin initiators who would have been eligible for RCT participation experienced slightly lower mean HbA1c reductions (-0.78%; 95% CI, -0.82% to -0.74%) compared with patients who would have been ineligible (-1.01%; 95% CI, -1.07% to -0.95%). Ineligible initiators had higher median (interquartile range) baseline HbA1c values than eligible initiators (8.5% [7.4% to 10.1%] vs 8.2% [7.6% to 9.8%]). In this cross-sectional study, more than half of empagliflozin initiators exhibited clinical characteristics that would have led to ineligibility for the RCTs leading to the drug's approval. While the findings suggest that the efficacy of empagliflozin in reducing HbA1c levels translates into real-world effectiveness, further studies should examine clinical outcome effectiveness and drug safety in routine clinical care.

Clinical Outcomes and Health-Related Quality of Life (HRQoL) Among Randomized Clinical Trial (RCT)-Eligible and RCT-Ineligible Patients: Results from the Connect® MM Registry

Clinical Outcomes and Health-Related Quality of Life (HRQoL) Among Randomized Clinical Trial (RCT)-Eligible and RCT-Ineligible Patients: Results from the Connect® MM Registry

Demographic Characteristics of Participants in Rheumatoid Arthritis Randomized Clinical Trials

Racial/ethnic minority groups, women, and elderly people experience a disproportionate burden of disease in rheumatoid arthritis (RA), making it particularly important to examine drug therapies in these populations. Despite a national health agenda to improve representation of diverse populations in randomized clinical trials (RCTs), there have been few large-scale analyses examining RCT demographic characteristics within rheumatology and none focusing on RA. To characterize the representation of racial/ethnic minority groups, women, and elderly people through a comprehensive systematic review of RA RCTs. A literature search of PubMed's MEDLINE database was conducted to identify RA RCTs in adults 19 years and older published in English between January 1, 2008, and January 1, 2018. Randomized double-blind RCTs examining any systemic, disease-modifying therapy were included. Secondary analyses of previously published RCTs were excluded. Of 1195 identified records, 240 articles (20.1%) met final selection criteria. The analysis focused on RCTs with at least 1 US-based site. Data were extracted and synthesized according to the PRISMA guidelines for systematic reviews. Studies were screened for eligibility criteria. Demographic data on the age, sex, and race/ethnicity of RCT participants were extracted. Data analysis was conducted from October 25, 2018, to March 15, 2019. Representation of race/ethnicity and sex, defined as the proportion of total participants that belonged to each racial/ethnic group or sex. Trends in proportions over time were examined and compared with US demographic data. A total of 240 RCTs with 77 071 participants were included. Of 126 RCTs with at least 1 US-based site (52.5%), the enrollment of minority racial/ethnic groups was significantly lower than their representation within the US Census population (16% vs 40%; P < .001), and the enrollment of men was significantly lower than the incidence of RA in men nationally (20.4% vs 28.6%; P < .001). There was no trend toward improved representation of racial/ethnic minority groups or men over time. Given the disproportionate burden of RA among racial/ethnic minority groups, it is imperative that policy makers better incentivize the inclusion of racial/ethnic minority groups in RA RCTs.

Variation in Asthma Clinical Trial Results by Environmental and Socioeconomic Exposures

PDS 64: Health impact assessment and environmental justice, Johan Friso Foyer, Floor 1, August 26, 2019, 1:30 PM - 3:00 PM Randomized clinical trials (RCTs) are generally considered the gold standard in medical research; by randomizing participants to treatment and control arms, they maximize internal validity and reduce between-group biases. RCTs, however, do not routinely examine variation by environmental and social exposures, which may impact clinical outcomes, treatment response, and generalizability. To assess whether variation in socioeconomic positon (SEP) and environmental exposures modify treatment response, we have developed and applied Geographic Information Systems (GIS)-based methods to three RCTs performed by the NIH AsthmaNet network, which is recruiting and implementing RCTs using the same protocols across 17 U.S. cities. In preliminary analyses, we have found that: (1) compared to race-specific U.S. averages, blacks recruited into AsthmaNet disproportionately live in impoverished census tracts; recruited whites disproportionately live in wealthier tracts. (2) At baseline, traffic density and SEP predicted variation in lung function, in the hypothesized directions. (3) In one trial, we found that near-residence roadway density explained greater variation in asthma symptoms than did corticosteroid use, and that children in higher-poverty areas had significantly shorter times to first corticosteroid use. We are now refining analyses of effect modification by near-residence roadway traffic and noise exposures, neighborhood violent crime, and health care access. Using spatial analysis and GIS to understand the lived context of RCT participants – better accounting for socioeconomic and environmental factors – may improve the interpretability and applicability of RCT results, by more clearly identifying subpopulations for whom a given intervention may be most effective.

Impact of Adding Telephone-Based Care Coordination to Standard Telephone-Based Smoking Cessation Counseling Post-hospital Discharge: a Randomized Controlled Trial.

Cessation counseling and pharmacotherapy are recommended for hospitalized smokers, but better coordination between cessation counselors and providers might improve utilization of pharmacotherapy and enhance smoking cessation. To compare smoking cessation counseling combined with care coordination post-hospitalization to counseling alone on uptake of pharmacotherapy and smoking cessation. Unblinded, randomized clinical trial PARTICIPANTS: Hospitalized smokers referred from primarily rural hospitals INTERVENTIONS: Counseling only (C) consisted of telephone counseling provided during the hospitalization and post-discharge. Counseling with care coordination (CCC) provided similar counseling supplemented by feedback to the smoker's health care team and help for the smoker in obtaining pharmacotherapy. At 6months post-hospitalization, persistent smokers were re-engaged with either CCC or C. Utilization of pharmacotherapy and smoking cessation at 3, 6, and 12months post-discharge. Among 606 smokers randomized, 429 (70.8%) completed the 12-month assessment and 580 (95.7%) were included in the primary analysis. Use of any cessation pharmacotherapy between 0 and 6months (55.2%) and between 6 and 12months (47.1%) post-discharge was similar across treatment arms though use of prescription-only pharmacotherapy between months 6-12 was significantly higher in the CCC group (30.1%) compared with the C group (18.6%) (RR, 1.61 (95% CI, 1.08, 2.41)). Self-reported abstinence rates of 26.2%, 20.3%, and 23.4% at months 3, 6, and 12, respectively, were comparable across the two treatment arms. Of those smoking at month 6, 12.5% reported abstinence at month 12. Validated smoking cessation at 12months was 19.3% versus 16.9% in the CCC and C groups, respectively (RR, 1.13 (95% CI, 0.80, 1.61)). Supplemental care coordination, provided by counselors outside of the health care team, failed to improve smoking cessation beyond that achieved by cessation counseling alone. Re-engagement of smokers 6months post-discharge can lead to new quitters, at which time care coordination might facilitate use of prescription medications. NCT01063972.