Generalizability Of Trials Research Articles

Generalizability of Clinical Trials of Novel Weight Loss Medications to the US Adult Population

This cross-sectional study investigates the extent to which individuals meeting label criteria for novel weight loss medications may not have been included in pivotal trials.

Underrepresentation of Racial and Ethnic Minorities in Metastatic Colorectal Carcinoma Clinical Trials within the United States.

To investigate if underrepresentation of racial and ethnic minorities exists in metastatic colorectal carcinoma (CRC) clinical trials. Representation of vulnerable subpopulations is essential for generalizability of clinical trials. Limited studies to date have investigated racial and ethnic representation of patients enrolled in clinical trials for metastatic CRC. ClinicalTrials.gov was queried for metastatic CRC clinical trials in the United States from 2000-2020. Incidence data were extracted from the SEER Database. Enrollment fraction (EF) was defined as number of trial participants divided by U.S. incidence of metastatic CRC in each race, ethnicity, and gender. Representation Quotient (RQ) was defined as the proportion of trial participants divided by proportion of U.S. metastatic CRC incidence for each subgroup. 8084 patients from 135 clinical trials were analyzed. 49.6% of clinical trials reported race data and 34.8% reported ethnicity data. Compared to 2000-2009, 2010-2019 had increased representation data reporting for race (61.2% vs. 38.8%) and ethnicity (64.6% vs. 35.4%). Of trials with race data, White patients represented 77.0%, Black patients 6.6%, Asian/Pacific Islander (API) patients 16.1%, American Indian/Alaska Native (AIAN) patients 0.2%, and Hispanic patients 6.8%. Black patients (median RQ 0.54), API patients (median RQ 0.19), AIAN patients (median RQ 0.00), and Hispanic patients (median RQ 0.26) were underrepresented. Black patients had a higher degree of underrepresentation in clinical trials with serum creatinine inclusion criteria (RQ 0.40 vs. 0.86, P=0.034). Strategies are needed to increase minority enrollment in clinical trials for metastatic CRC. Identification of systemic barriers is integral in public policy advocacy to increase representation.

Overcoming racial and ethnic disparities in clinical trial enrollment real world evidence from an NCI-Designated Cancer Center in a minority majority county.

e13708 Background: Significant racial and ethnic disparities continue to persist in clinical trial enrollment. Specifically, Asian and Hispanic individuals are severely underrepresented compared to their census estimates and make up as little as 1% and 6% respectively of all clinical trial enrollments [PMID: 35875251]. This limits the generalizability of clinical trials and consequently the application of novel therapeutics for diverse populations. This observational study looks at enrollment demographics at the University of California, Irvine (UCI) with an emphasis on minority participation in clinical trials. We hypothesized that minorities would be underrepresented in our enrollment population. Methods: The UCI Chao Family Comprehensive Cancer Center (CFCCC) is located in Orange County (OC), CA, a minority-majority county. Enrollment data from clinical trials was collected from 2015-2023 through the CFCCC clinical research database. Demographics were compared to data provided by the NIH SEER reports in both OC and United States. Results: Between 2015-2023, 2315 individuals across 3 UCI Health facilities were enrolled. Demographics were as follows: White, Asian, Black, American Indian/Alaska Native, mixed/unknown race (66.4%/20.1%/2.4%/0.7%/0.7%/ 9.3%). Non-Hispanic vs Hispanic ethnicity (77.8%/20.6%). Female vs Male sex (47.6%/52.3%). Age <70 vs >70 years (78.6%/21.4%). Low Income/Health Professional Shortage Areas (HPSA) vs non-Low Income/HPSA (44.9%/55.0%). Study Phase: Phase I/II (39.2%), Phase II (28.0%), Phase III (29.3%), Phase II/III (3.0%), and Phase IV (0.3%). Study sponsor: Industry (61.2%), Investigator initiated (23.5), Cooperative group (14.9%), other (0.3%). Most notably, the Asian enrollment (20.1%) and Hispanic enrollment (20.6%) exceeded demographic representation of Asians (15.6%) and Hispanics (17.3%) in OC. Conclusions: Our results demonstrate that accrual of minorities is feasible across all types of clinical trials. These findings suggest that minorities are not inherently less likely to enroll in clinical trials. A clinical trial portfolio mirroring the catchment area might improve accrual of minorities. Enrollment based on race/ethnicity and trial phase/sponsor will be presented at the meeting.

Pragmaticism in Cancer Clinical Trials.

Clinical trials are essential for advancing oncology treatment strategies and have contributed significantly to the decline in cancer mortality rates over the past decades. Traditional explanatory trials, focused on establishing intervention efficacy in ideal settings, often lack generalizability and may not reflect real-world patient care scenarios. Furthermore, increasing complexity in cancer clinical trial design has led to challenges such as protocol deviations, slow enrollment leading to lengthened durations of trial, and escalating costs. By contrast, pragmatic trials aim to assess intervention effectiveness in more representative patient populations under routine clinical conditions. Here, we review the principles, methodologies, challenges, and advantages of incorporating pragmatic features (PFs) into cancer clinical trials. We illustrate the application of pragmatic trial designs in oncology and discuss the QUASAR collaborative, TAPUR study, and the ongoing PRAGMATICA-LUNG trial. Although not all oncology trials may be amenable to adopting fully pragmatic designs, integration of PFs when feasible will enhance trial generalizability and real-world applicability. Project Pragmatica and similar initiatives advocate for the integration of real-world practice with clinical trials, fostering a nuanced approach to oncology research that balances efficacy and effectiveness assessments, ultimately with a goal of improving patient outcomes.

Testing the external validity of the POUT III trial (adjuvant platnium-based chemotherapy in upper tract urothelial carcinoma) in a North American cohort

ObjectiveThe European POUT III randomized controlled trial provided level-one evidence that adjuvant platinum-based chemotherapy is the standard of care following nephroureterectomy (RNU) for locally invasive or node-positive upper tract urothelial carcinoma. We aim to assess this European randomized controlled trial's generalizability (external validity) to a North American cohort, using a nationwide database. Materials and MethodsTo compare trial patients with those seen in real-world practice, we simulated the trial inclusion criteria using data from the National Cancer Database (NCDB). We identified patients with histologically confirmed transitional cell carcinoma who underwent RNU. The available demographic characteristics of the NCDB cohort were compared with the POUT III trial cohort using Chi-squared test. ResultsThe NCDB cohort (n = 3,380) had a significantly higher proportion of older patients (age ≥ 80: 23.5% vs. 5%), and more males (68% vs. 56.2%) than the POUT cohort (Table 1, both p < 0.001). Additionally, the rate of advanced nodal disease was higher in the NCDB (N1 9.6%, N2 9.3%) than in the POUT (N1 6%, N2 3%) cohort (p < 0.001). A more extensive lymph node dissection was performed in NCDB vs. POUT patients (node≥10 10.9% vs. 3%, p < 0.001). Sensitivity analysis removing all subjects with a Charlson Comorbidity Index > 0 did not change the significance of any results. ConclusionsWhile the primary disease stage was similar, the rate of advanced nodal disease was significantly higher in NCDB, which might be explained partially by the more extensive lymph node dissection performed in the latter. These differences warrant caution when applying the POUT III findings to North American patients.

Pragmatism in manual therapy trials for knee osteoarthritis: a systematic review.

Manual therapy is an often-utilized intervention for the management of knee osteoarthritis (OA). The interpretation of results presented by these trials can be affected by how well the study designs align applicability to real-world clinical settings. To examine the existing body of clinical trials investigating manual therapy for knee OA to determine where they fall on the efficacy-effectiveness spectrum. This systematic review has been guided and informed by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Randomized controlled trials that investigated manual therapy treatments for adults with knee OA were retrieved via searches of multiple databases to identify trials published prior to April 2023. The Rating of Included Trials on the Efficacy-Effectiveness Spectrum (RITES) tool was used to objectively rate the efficacy-effectiveness nature of each trial design. The Cochrane Risk of Bias 2.0 assessment tool (RoB-2) was used to assess the risk of bias across five domains. Of the 36 trials, a higher percentage of trials had a greater emphasis on efficacy within all four domains: participant characteristics (75.0%), trial setting (77.8%), flexibility of intervention (58.3%), and clinical relevance of experimental and comparison intervention (47.2%). In addition, 13.9% of the trials had low risk of bias, 41.7% had high risk of bias, and 44.4% had some concerns regarding bias. While many trials support manual therapy as effective for the management of knee OA, a greater focus on study designs with an emphasis on effectiveness would improve the applicability and generalizability of future trials.

(198) Gaps in Patient Representation for Peyronie’s Disease Clinical Trials

Abstract Introduction Recent studies have highlighted the lack of generalizability of clinical trials with respect to patient race and ethnicity for urologic diseases due to inadequate recruitment and reporting of racial and ethnic minority populations in clinical trials. To date, there have been no studies examining the diversity of patients with Peyronie’s disease recruited to clinical trials. Objective The objective of this study was to identify disparities in representation of patients in PD clinical trials relating to race and ethnicity. Methods A systematic electronic search of the published English literature was performed to identify clinical trials involving PD. The search was performed using the Medline/Pubmed, Ovid, and Embase databases. After articles were identified, they were screened based on their title and abstract. Articles were included if they were in English, relevant to Peyronie’s disease and specified clinical trial in the title or abstract. Exclusion criteria were articles about congenital penile curvature, systematic reviews, pooled analysis, and articles not in the English language. Results Of the 48 articles included in the analysis, 10 of them reported race, ethnicity, or sexual orientation. All 10 studies reported enrollment of Caucasian men, with Caucasian men making up 98.0% of the enrolled population across these 10 studies. Enrollment of African-American men were was reported in six of the 10 studies and constituted 2.6% of the enrollees. Enrollment of Asian men were was reported in three studies and comprised of 0.7% of the patients in those studies. Enrollment of American Indian/Native American men were was reported in a single study and made up 0.2% of patients enrolled in that study. Hispanic ethnicity was the only ethnicity reported and was available in five studies with of 4.0% of men reported as Hispanic across those studies. Only two studies reported the sexual orientation of patients. Five of the 10 studies that reported race enrolled patients exclusively from the United States. A pooled analysis from these 5 studies revealed that Caucasian men were significantly overrepresented and all other racial and ethnic groups were significantly underrepresented (p &amp;lt; .05). Conclusions In conclusion there is a lack of representation of multiple racial and ethnic minorities with PD along with the over-representation of Caucasian men. Aside from the lack of reporting of racial and ethnic information, there was a dearth of information on sexual orientation of men in these clinical trials. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast, Boston Scientific.

Generalizability of clinical trial efficacy results to a real-world population: An example in migraine prevention.

Health care decision makers are often concerned about the external validity of randomized controlled trials (RCTs), as their results may not apply to certain patients in the real world who intend to receive treatment. To demonstrate a methodology for assessing the generalizability of clinical trial results to a real-world population, before sufficient and appropriate real-world effectiveness data are available, using individual patient-level data from an RCT and aggregated baseline data from a real-world French registry in migraine. The analyses were conducted in 2 steps. First, individual patient-level baseline data from the multinational CONQUER RCT were weighted to match aggregated real-world InovPain registry patient characteristic data. Matched patient characteristics were sex, age, migraine type and duration, number of monthly migraine headache days, and number of monthly headache days at baseline. Second, the weighted CONQUER patient data were used to reanalyze the primary endpoint of CONQUER (least squares mean change from baseline in the number of monthly migraine headache days during the 3-month double-blind treatment phase) using predefined methodology. Sensitivity analyses were conducted to assess the robustness of findings. A total of 462 patients with migraine were randomized and treated with galcanezumab or placebo in CONQUER; aggregated InovPain data were available from 130 patients with migraine. We identified no important differences in baseline patient characteristics between the 2 prespecified populations, suggesting good external validity for CONQUER. Although this limited the extent of observed differences between the original and matched CONQUER populations, weighting of CONQUER data did help harmonize the 2 datasets and allow the results obtained in CONQUER to be generalized to patients more representative of the real-world French population with migraine. Results of weighted analyses suggested that galcanezumab would be superior to placebo for reducing monthly migraine headache days in a clinical trial in patients with episodic or chronic migraine who reflected the characteristics of patients eligible to receive the drug in France. Findings suggest that our methods may be helpful for assessing the generalizability of clinical trial results to a real-world population before the availability of substantial real-world clinical data.

Is nonoperative management of appendicitis safe and effective in multi-morbid patients?

BackgroundThe purpose of this study was to (1) compare post-treatment outcomes of operative and nonoperative management of acute appendicitis in multi-morbid patients and (2) evaluate the generalizability of prior clinical trials by determining whether outcomes differ in multi-morbid patients compared to the young and healthy patients who resemble prior clinical trial participants. MethodsWe conducted a retrospective cohort study using the National Inpatient Sample from 2004 to 2017. We included 368,537 patients with acute, uncomplicated appendicitis who were classified as having 0 or 2+ comorbidities. We compared inpatient morbidity, mortality, length of stay, and costs using propensity scores. Unmeasured confounding was addressed with probabilistic sensitivity analysis. ResultsOverall, 5% of patients without comorbidities were treated nonoperatively versus 20% of multi-morbid patients. Compared to surgery, nonoperative management was associated with a 3.5% decrease in complications (95% confidence interval 3%–4%) for multi-morbid patients, but there was no significant difference for patients without comorbidity. However, nonoperative management was associated with a 1.5% increase in mortality for multimorbid patients (95% confidence interval 1.3%–1.7%). Costs and length of stay were lower for all patients treated with surgery. Probabilistic sensitivity analysis showed that results were robust to the effects of unmeasured confounding. ConclusionOur results raise concerns about the generalizability of clinical trials that compared nonoperative and operative management of appendicitis because (1) those trials enrolled mostly young and healthy patients, and (2) results in multi-morbid patients differ from outcomes in younger and healthier patients.

Engaging Underrepresented Patients in Hematology Clinical Trials through the LLS Impact (Influential Medicine Providing Access to Clinical Trials) Research Grant: A Multi-Institutional Effort

Introduction: Despite governmental and industry-sponsored efforts, clinical trial participation among rural residents and racial and ethnic minorities remains low. The NIH Revitalization Act of 1993 directed the NIH to establish guidelines for inclusion of women and minorities in clinical research. In 2015, the Food and Drug Administration launched an action plan to improve the quality of demographic subgroup data collection, identify barriers to enrollment, employ strategies to increase participation, and promote transparency of related data. However subsequent studies (Green et al. Health Aff. March 2022, Kanapuru et al. Blood Advances. March 2022.) showed no improvement in participation of racial minorities, including Blacks and Hispanics since this plan was enacted. Various complex system- and individual-based factors, including lack of clinical trial availability; lack of diversity in the investigator work force; scant patient and provider awareness of clinical trials; lack of trust in the health care system; and issues with access to care-often driven by financial, geographic, or social constraints (Allison et al. Cureus. Apr 2022.), and stringent eligibility criteria are deemed responsible. The Leukemia &amp; Lymphoma Society (LLS) IMPACT (Influential Medicine Providing Access to Clinical Trials) research grant strives to bridge this unrelenting care gap. Methods: The LLS IMPACT program includes a 5-year research grant which was launched in 2021. The IMPACT grants support the establishment of clinical trial networks involving academic cancer centers (“Hubs”) linked to community clinics and oncology centers (“Spokes”). The program's overall goal is to provide patients access to trials through participation at the community sites. Initially, 3 institutional sites were selected to participate. These institutions had unique and tailored strategies to improve engagement of underrepresented patients, including black, indigenous, people of color, Hispanic, Latina/Latino, and people from rural communities in vastly different climates and local cultures. The IMPACT grant expanded to encompass 4 additional sites given the imminent needs and clamor of the hematology clinical trials community (Figure 1A). The catchment areas and strategies employed at each institution are summarized in the table (Figure 1B). Results: At the start of the grant period, focus was on building clinical research infrastructure and opening non-interventional clinical trials to teach personnel about clinical research and create relationships with patients. Other programs such as webinar series, tumor boards, technological advancements, and educational workshops were also established to enhance engagement among physicians, match patients to clinical trials, and to provide clinical trial education to potential patients. One trial that has seen early success is the CHIVE IMPACT trial, a non-interventional registry and biorepository which has enrolled 24 patients at a rural and underserved site as of July 2023. The purpose of CHIVE is to enroll patients who have clonal hematopoiesis (CH) or are at risk of CH and follow prospectively in efforts to understand risk of progression and potential for early intervention. The Universal Protocol is another biorepository trial which has more than tripled its enrollment number at a community site between 2021 and 2022. Of the 63 patients enrolled in 2022, 66% of them identified as a race other than White. As our core goal is to increase access to interventional trials, we hope to bring industry sponsored phase II and phase III studies to underrepresented areas that serve a broad patient population. Lack of financial resources, lack of transportation and distance to trial sites, and residual distrust of the medical community (e.g., legacy of Tuskegee experiments) are barriers the grantees are focused on overcoming to enroll the intended populations into clinical trials. Conclusion: The innovative strategies employed to expand access to clinical trials for underrepresented population at the various institutions through the LLS's IMPACT research grant can be utilized during clinical trials design and implementation phases to improve generalizability of clinical trials in hematologic malignancies. In the third year of this program, 7 participating sites are engaging impactful strategies (Figure 1B) which will be reported at the end of the grant period.

Abstract 18956: Knowledge of and Attitude Towards Clinical Trials Among Women in Rural Areas: A Survey-Based Study

Introduction: In evidence-based era of cardiology with emerging of potential therapies, it is crucial to include diverse population in terms of (geography, gender, race, and economic status) in clinical trials (CT) to enhance generalizability of trials results. Such inclusion necessitates exploring barriers and motivators of diverse population for participation in CT. There is lack of data from Middle Eastern countries regarding perspectives of population about CT. Furthermore, there is no data about perceptions of Iraqi population in general and women in particular regarding CT. Research question: We aim to explore knowledge and perceptions of female patients about CT. Methods: Paper-based survey was filled by investigators during face-to-face interview with women attending healthcare facilities in a rural area in Iraq. Results: n=50, mean age=28.7 year, 50% had primary education level. 36% defined CT as experiments to test a new drug or procedure. Main concerns to participate in CT was safety 62%. 32% said they would participate in CT if they were asked to. 20% said they will participate in CT involving surgery or procedure if were asked to. 80% reported they would participate in education CT (CT involving telemedicine/video programs as intervention). Although all participants never participated in CT before, 80% had concerns about CT in general. 34% of women thought that family duties could prevent them from commitment with trials. 70% agreed to participate in clinical trials if drug safety was ensured, while 90% refused to participate in trials if the drug had unknown safety. 86% of participants agree to participate in trials if it was open label. Conclusions: Safety was a major concern of respondents for participation in CT. Establishing patient public involvement is essential step towards initiating CT ecosystem in Iraq. Being aware of population perceptions and concerns are critical to include this under-represented population in cardiovascular CT.

Multi-Level Factors Underlying Racial/Ethnic Inequities in Clinical Trial Participation Among Patients with Hematologic Cancers: Lessons for the Development of Diversity Plans

Background: The US Food &amp; Drug Administration announced that drug sponsors will be required to implement plans to improve racial/ethnic diversity in clinical trials starting in 2024. While historically marginalized racial/ethnic populations are less likely to participate in cancer trials, there is limited information regarding inequities in access to hematologic cancer trials. It is also unknown whether social determinants of health (SDOH) explain racial/ethnic inequities in trial participation. Here we examined the extent to which commonly used trial inclusion criteria and SDOH factors explain racial/ethnic inequities in clinical trial participation among patients with six hematologic cancers. Methods: This retrospective study used the nationwide Flatiron Health electronic health record-derived de-identified database (2011-2022) of adult patients with multiple myeloma, non-Hodgkin's lymphoma (diffuse large B-cell, follicular, or mantle cell lymphoma) or leukemia (chronic lymphocytic or acute myeloid leukemia). Area-level SDOH ( e.g. predominant race/ethnicity - a measure of segregation) characterizing where patients lived were assessed using the American Community Survey census tract data. Patients were followed from initial diagnosis to clinical study drug receipt (a proxy for trial participation), death, or last recorded activity. Associations of race/ethnicity and SDOH factors with trial participation were assessed using cause-specific hazards models adjusted for clinical confounders (diagnosis year, age, sex, and cancer type). To determine which commonly used trial inclusion criteria ( i.e. abnormal creatinine serum [≥ 2] and performance status) and SDOH factors underlie racial/ethnic inequities, mediation analysis was performed using nonlinear multiple additive regression tree models. Results: This study included 51,382 patients (median age: 67 years, 42.2% women; 57.7% non-Latinx [NL] White, 6.9% NL Black, 6.1% Latinx, 29.4% other/unknown). Black and Latinx patients were more likely to live in marginalized areas ( e.g. segregated neighborhoods color and higher percentages of limited English proficiency and low vehicle ownership) than White patients. Overall, 5.6% of patients participated in trials. Patients who received care from community practices or lived in marginalized neighborhoods were less likely to participate in trials. Black (4.2%; hazard ratio [HR] 0.62, 95% confidence interval [CI]: 0.52- 0.73) and Latinx patients (3.7%; HR 0.53, CI: 0.44-0.65) were less likely to participate in trials than White patients (6.4%). Black-White trial inequities were mediated (77%, CI: 42%-117%) by practice type ( e.g., community vs. academic center, 19%, CI: 9%-28%) and area-level SDOH such as segregation (49%, CI: 21%-77%) and vehicle ownership (12%, CI: 1%-24%). Mediators explained 55% (CI: 23%-87%) of the Latinx-White trial participation inequity; area-level SDOH-including segregation (30%, CI: 3%-58%), limited English proficiency (21%, CI: -3% to 45%), and vehicle ownership (17%, CI: 0%-45%)-were the most important mediators. Clinical factors did not substantially mediate racial/ethnic inequities (&amp;lt; 3% proportion mediated). Conclusion: Black and Latinx patients diagnosed with hematologic cancers are 40% to 50% less likely to participate in clinical trials than their White counterparts. SDOH factors explained most of these inequities. These findings suggest that efforts to increase racial/ethnic diversity in cancer trials must address the persistent effects of segregation, along with everyday obstacles to clinical care, such as transportation and language barriers. Without concerted efforts to increase trial participation among historically marginalized racial/ethnic groups, trials may perpetuate inequities in investigational drug access and adversely impact the generalizability of pivotal cancer treatment trials.

Strategies for Improving Enrollment of Diverse Populations with a Focus on Lipid-Lowering Clinical Trials.

We review under-representation of key demographic groups in cardiovascular clinical trials, focusing on lipid-lowering trials. We outline multilevel strategies to recruit and retain diverse populations in cardiovascular trials. Barriers to participation in trials occur at the study, participant, health system, sponsor, and policy level, requiring a multilevel approach to effectively increase participation of under-represented groups in research. Increasing the representation of marginalized and under-represented groups in leadership positions in clinical trials can ensure that their perspectives and experiences are considered. Trial design should prioritize patient- and community-indicated needs. Women and individuals from racially/ethnically diverse populations remain under-represented in lipid-lowering and other cardiovascular clinical trials relative to their disease burden in the population. This limits the generalizability of trial results to the broader population in clinical practice. Collaboration between community stakeholders, researchers, and community members can facilitate shared learning about trials and build trust.

Review of therapeutic trends in clinical trials for hidradenitis suppurativa: therise of biologics and demographic under-representation.

We assessed interventional clinical trials for hidradenitis suppurativa from 2006 to 2021 noting patient demographics, intervention types and reported outcomes. We report and analyse the emerging trend towards biologic treatments. We also discuss that across studies, more consistent documentation of patient characteristics as well as more variable intervention types may broaden trial generalizability and provide benefit to more patients.

Profound impact of ECOG performance status on clinical trial eligibility and access: Diverging effects by cancer type.

97 Background: The Eastern Cooperative Oncology Group (ECOG) performance status is a widely used measure of a patient's (pt) physical function and is often used as a criterion for clinical trial eligibility. Strict use of this criterion may exclude pts with comorbidities or poorer performance status, limiting the generalizability of trial results to the broader cancer pt population. This study aimed to evaluate the impact of ECOG performance status on eligibility for solid and non-solid cancer clinical trials (CTs) among pts using the Leal web-based platform. Methods: Leal (formerly, Trialjectory) is an AI-based platform that matches cancer pts to CTs based on a self-reported questionnaire that generates an individual clinical profile. The profile includes parameters essential for CT matching such as disease status, stage, biomarkers, treatment history, comorbidities and demographics. Data from pts with solid and non-solid cancers were analyzed. The number of matched trials per pt was determined based on the pt’s profile, location and travel preference. To assess the impact of ECOG score, the data set was edited to reflect a better performance status per pt. We used Yuen’s robust paired samples analysis to assess the association between improving the ECOG score and the number of matched CTs. Moreover, we have collected the cumulative ECOG distribution as an eligibility criteria in CTs in various cancer types. Results: In a data set of 5,018 cancer pts, high ECOG score (3 or 2) was significantly associated with fewer matched clinical trials per pt (p&lt;0.001). This relationship was independent of ethnicity and gender. The relationship varied by cancer type, with a 3-fold greater effect size in solid tumors compared to non-solid tumors. When ECOG score per pt was edited from 3 to 2 or from 2 to 1, the number of matched CTs significantly increased by 246% and 189%, respectively, for all cancer types (p&lt;0.001). Notably, the prevalence of CTs that allow worse ECOG scores (2 or higher) was significantly higher in non-solid CTs compared to solid tumors (p&lt;0.001). Conclusions: Our results show that strict ECOG scores are significantly associated with fewer matched CTs per pt. This relationship varies by cancer type, with a greater impact on solid tumors. These findings suggest that cancer type may influence the relationship between ECOG scores and access to CTs. Pts with solid tumors may face more barriers to trial enrollment due to strict ECOG requirements. Our results highlight the need for a more nuanced approach to using ECOG performance status as an eligibility criterion in CTs, taking into account the specific cancer type and its associated physical demands. Further research is needed to fully understand the impact of ECOG performance status on trial enrollment and to determine the optimal balance between pt safety and representation in clinical research.

Neighborhood socioeconomic disadvantage measures in rehabilitation clinical trials: Lessons learned in recruitment

PurposeThe Area Deprivation Index (ADI) measures the relative disadvantage of an individual or social network using US Census indicators. Although a strong re-hospitalization predictor, ADI has not been routinely incorporated into rehabilitation research. The purposes of this paper are to examine the use of ADI related to study recruitment, association with carepartner psychosocial factors, and recruitment strategies to increase participant diversity. MethodsDescriptive analysis of baseline data from a pilot stroke carepartner-integrated therapy trial. Participants were 32 carepartners (N = 32; 62.5 % female; mean age 57.8 ± 13.0 years) and stroke survivors (mean age (60.6 ± 14.2) residing in an urban setting. Measures included ADI, Bakas Caregiver Outcome Scale, Caregiver Strain Index, and Family Assessment Device. ResultsMost carepartners were Non-Hispanic White participants (61.3 %), part or fully employed (43 %), with >$50,000 (67.7 %) income, and all had some college education. Most stroke survivors were Non-Hispanic White participants (56.3 %) with some college (81.3 %). Median ADI state deciles were 3.0 (interquartile range 1.5–5, range 1–9), and mean national percentiles were 41.7 ± 23.5 with only 6.3 % of participants from the most disadvantaged neighborhoods. For the more disadvantaged half of the state deciles, the majority were Black or Asian participants. No ADI and carepartner factors were statistically related. ConclusionsThe use of ADI data highlighted a recruitment gap in this stroke study, lacking the inclusivity of participants from disadvantaged neighborhoods and with lower education. Using social determinants of health indicators to identify underrepresented neighborhoods may inform recruitment methods to target marginalized populations and broaden the generalizability of clinical trials.

Exploring the Effect of Eligibility Criteria on AD Severity and Severe Adverse Event in Eligible Patients.

Clinical trials were vital tools to prove the effectiveness and safety of medications. To maximize generalizability, the study sample should represent the sample population and the target population. However, the clinical trial design tends to favor the evaluation of drug safety and procedure (i.e., internal validity) without clear knowledge of its penalty on trial generalizability (i.e., external validity). Alzheimer's Disease (AD) trials are known to have generalizability issues. Thus, in this study, we explore the effect of eligibility criteria on the AD severity patients and the severe adverse event (SAE) among the eligible patients.

Generalizability of cognitive results from clinical trial participants to an older adult population: Addressing external validity.

Study inclusion criteria and recruitment practices limit the generalizability of randomized-controlled trial (RCT) results. Statistical modeling could enhance generalizability of outcomes. To illustrate this, the cognition-depression relationship was assessed with and without adjustment relative to the target population of older women. Randomized participants from four RCTs and non-randomized participants from two cohorts were included in this study. Prediction models estimated probability of being randomized into trials from target populations. These probabilities were used for inverse odds weighting relative to target populations. Weighted linear regression was used to assess the depression-cognition relationship. There was no depression-cognition relationship in the combined randomized sample. After applying weights relative to a representative cohort, negative relationships were observed. After applying weights relative to a non-representative cohort, bias of estimates increased. Quantitative approaches to transportability using representative samples may explain the absence of a-priori established relationships in RCTs.

Current landscape of clinical trials for vitiligo: improving outcome standardization and trial diversity.

We assessed interventional clinical trials for vitiligo from 2015 to 2021 noting patient demographics, intervention types and reported outcomes. We discuss that across studies, more consistent documentation of patient characteristics as well as more variable intervention types may broaden trial generalizability and provide benefit to more patients.

Loss to Follow-up in Head and Neck Cancer: A Systematic Review of Randomized Controlled Trials.

To evaluate the reporting and rates of loss to follow-up (LTFU) in head and neck cancer (HNC) randomized controlled trials based in the United States. Pubmed/MEDLINE, Cochrane, Scopus databases. A systematic review of titles in Pubmed/MEDLINE, Scopus, and Cochrane Library was performed. Inclusion criteria were US-based randomized controlled trials focused on the diagnosis, treatment, or prevention of HNC. Retrospective analyses and pilot studies were excluded. The mean age, patients randomized, publication details, trial sites, funding, and LTFU data were recorded. Reporting of participants through each stage of the trial was documented. Binary logistic regression was performed to evaluate associations between study characteristics and reporting LTFU. A total of 3255 titles were reviewed. Of these, 128 studies met the inclusion criteria for analysis. A total of 22,016 patients were randomized. The mean age of participants was 58.6 years. Overall, 35 studies (27.3%) reported LTFU, and the mean LTFU rate was 4.37%. With the exception of 2statistical outliers, study characteristics including publication year, number of trial sites, journal discipline, funding source, and intervention type did not predict the odds of reporting LTFU. Compared to 95% of trials reporting participants at eligibility and 100% reporting randomization, only 47% and 57% reported on withdrawal and details of the analysis, respectively. The majority of clinical trials in HNC in the United States do not report LTFU, which inhibits the evaluation of attrition bias that may impact the interpretation of significant findings. Standardized reporting is needed to evaluate the generalizability of trial results to clinical practice.