Enrollment In Research Studies Research Articles

Exploring Health Care Disparities in Genetic Testing and Research for Hereditary Cardiomyopathy: Current State and Future Perspectives.

Background Hereditary cardiomyopathies are commonly occurring myocardial conditions affecting heart structure and function with a genetic or familial association, but the etiology is often unknown. Cardiomyopathies are linked to significant mortality, requiring robust risk stratification with genetic testing and early diagnosis. Hypothesis We hypothesized that health care disparities exist in genetic testing for hereditary cardiomyopathies within clinical practice and research studies. Methods In a narrative fashion, we conducted a literature search with online databases such as PubMed/MEDLINE, Google Scholar, EMBASE, and Science Direct on papers related to hereditary cardiomyopathies. A comprehensive analysis of findings from articles in English on disparities in diagnostics and treatment was grouped into four categories. Results Racial and ethnic disparities in research study enrollment and health care delivery favor White populations and higher socioeconomic status, resulting in differences in the development and implementation of effective genetic screening. Such disparities have shown to be detrimental, as minorities often suffer from disease progression to heart failure and sudden cardiac death. Barriers related to clinical genetic testing included insurance-related issues and health illiteracy. The underrepresentation of minority populations extends to research methodologies, as testing in ethnic minorities resulted in a significantly lower detection rate and diagnostic yield, as well as a higher likelihood of misclassification of variants. Conclusions Prioritizing minority-based participatory research programs and screening protocols can address systemic disparities. Diversifying research studies can improve risk stratification strategies and impact clinical practice.

Patient-Associated Survival Modulators in Adolescent and Young Adult (AYA) Patients (Pts) with Acute Myeloid Leukemia (AML)

Background: AML is a highly aggressive hematologic malignancy, but the AYA pts [aged 18-39 years (y)] have improved survival, with ~50% of pts achieving long-term cure. Pt outcomes are known to be affected by disease-related factors including cytogenetic findings and gene mutations, which were established in large genomic studies. In addition, pt-related factors, such as self-reported race and socioeconomic contributors have been found to affect survival in population-based studies. Whereas population-based studies are performed on large pt cohorts to establish meaningful conclusions, they usually lack details with respect to additional pt-related factors, including complete comorbidities, insurance status as well as information on disease presentation, such as time from the first provider contact to confirmation of AML diagnosis (time to diagnosis) and treatment, which might also influence pt survival. Rationale and Methods: Thus, we set out to establish recent survival rates of AML AYA pts at the population level using pts reported to one of 12 Surveillance Epidemiology End Results (SEER) Program registries of the National Cancer Institute [n=1119; median age, 30 y,1992-2014; n=239; median age, 29 y, 2015-2020], and analyze possible factors influencing survival. In parallel, we performed an in-depth analysis of treatment response and survival, including time to diagnosis, and additional pt-associated variables pertinent to AYA pts (employment status, housing, insurance, comorbidities, distance to treatment center, research study enrollment, biobanking) based on retrospectively collected data of AYA AML pts cared for at a major US Comprehensive Cancer Center (CCC) in 2015-2020 (n=96, median age, 31 y), for whom detailed clinical information was available. Results: Generally, overall survival (OS) of AYA AML pts significantly improved over time, with a marked improvement of 3-y OS rates from 47% in pts diagnosed prior to 2009, to 63% in pts diagnosed in 2010-2014 and 69% in pts diagnosed in 2015-2020. Analysis of possible associations between demographic parameters and risk of death among AYA AML pts reported to SEER Program registries did not show any statistically significant impact of sex, age, county-level median household income or metro/rural status. The only factor affecting OS of AYA AML pts was race. Specifically, Black AML pts had a higher risk of death compared with that of White AML pts [HR 2.13 (95% CI 1.03 - 4.39)], with 3-y OS rates of 47% and 80% ( P=.04), respectively. Survival disparities did not improve over time. CCC AYA AML pts had similar OS rates to those seen in the population-based analyses, with a 3-y OS rate of 70%. Ninety-three percent of pts achieved a complete remission, and 31% of pts relapsed. Analyses of CCC AML pts allowed for preliminary assessment of additional parameters. Ninety-one percent of pts (77/85) received a diagnosis in ≤2 weeks after first provider contact. Although pt numbers were small, there was a trend for a longer diagnosis time in Black pts, 27% (3/11) of whom were diagnosed >2 weeks after first presentation, compared with only 8% (5/61; P=.10) of White pts. Interestingly, analysis of possible additional outcome modulators in CCC AYA pts suggested that presence of other medical conditions at diagnosis associated with lower relapse rates (16% vs 34%, P=.04), and unemployment tended to associate with higher relapse rates (34% vs 17%, P=.06). In addition, of pts approached for biobanking, fewer Black pts consented to sample collection than White pts (60% vs 87%, P=.06). Conclusion: Survival of AYA pts with AML significantly improved over time, likely driven by availability of allogeneic stem cell transplantation and improved supportive care. Black race still represents the most important negative survival prognosticator, without marked signs of improvement. An exploratory analyses of additional pt-associated variables suggested less recognized factors that may impact survival, such as trends for longer time to diagnosis and reduced participation in biobanking protocols in Black pts compared with White pts, and a higher relapse rate in pts who are unemployed. Although these differences were not yet statistically significant , we are currently in the process of increasing the sample size to further evaluate these potentially important trends. Support: American Cancer Society, Leukemia Lymphoma Society

Gathering the Stakeholder's Perspective: Experiences and Opportunities in Rare Genetic Disease Research.

Research participant feedback is rarely collected; therefore, investigators have limited understanding regarding stakeholders' (affected individuals/caregivers) motivation to participate. Members of the Genes to Mental Health Network (G2MH) surveyed stakeholders affected by copy number variants (CNVs) regarding perceived incentives for study participation, opinions concerning research priorities, and the necessity for future funding. Respondents were also asked about feelings of preparedness, research burden, and satisfaction with research study participation. Modified validated surveys were used to assess stakeholders´ views across three domains: (1) Research Study Enrollment, Retainment, Withdrawal, and Future Participation; (2) Overall Research Experience, Burden, and Preparedness; (3) Research Priorities and Obstacles. Top box score analyses were performed. A total of 704 stakeholders´ responded from 29 countries representing 55 CNVs. The top reasons for initial participation in the research included reasons related to education and altruism. The top reasons for leaving a research study included treatment risks and side effects. The importance of sharing research findings and laboratory results with stakeholders was underscored by participants. Most stakeholders reported positive research experiences. This study provides important insight into how individuals and families affected with a rare CNV feel toward research participation and their overall experience in rare disease research. There are clear targets for areas of improvement for study teams, although many stakeholders reported positive research experiences. Key findings from this international survey may help advance collaborative research and improve the experience of participants, investigators, and other stakeholders moving forward.

Exclusion of females in autism research: Empirical evidence for a "leaky" recruitment-to-research pipeline.

Autism spectrum disorder (ASD) is characterized by challenges in social communication and the presence of repetitive behaviors or restricted interests. Notably, males are four times as likely as females to be diagnosed with autism. Despite efforts to increase representation and characterization of autistic females, research studies consistently enroll small samples of females, or exclude females altogether. Importantly, researchers often rely on standardized measures to confirm diagnosis prior to enrollment in research studies. We retrospectively analyzed the effects of one such measure (Autism Diagnostic Observation Schedule, ADOS) on research inclusion/exclusion rates by sex in autistic adults, all of whom had a preexisting community diagnosis of autism (n=145, 95 male, 50 female). Using the ADOS as a confirmatory diagnostic measure resulted in the exclusion of autistic females at a rate over 2.5 times higher than that of autistic males. We compared sex ratios in our sample to those in other large, publically available datasets that rely either on community diagnosis (6 datasets, total n=42,209) or standardized assessments (2 datasets, total n=214) to determine eligibility of participants for research. Reliance on community diagnosis rather than confirmatory diagnostic assessments resulted in significantly more equal sex ratios. These results provide evidence for a "leaky" recruitment-to-research pipeline for females in autism research. LAY SUMMARY: Despite efforts to increase the representation of autistic females in research, studies consistently enroll small samples of females or exclude females altogether. We find that despite making up almost 50% of the initially recruited sample based upon self-report of community diagnosis, autistic females are disproportonately excluded from research participation as a result of commonly used autism diagnostic measures. In our sample, and several other publically available datasets, reliance on community diagnosis resulted in significantly more equal sex ratios.

Improve Eczema/Asthma Research Study Enrollment and Retention Using Engaging, Participant Co-designed Graphic-Style Stories

Stories are powerful tools to increase understanding of complex information, encourage engagement and activate learning and positive behavior change. We hypothesized that sharing of participant co-designed graphic-style stories with caregivers of pediatric research participants wound improve study enrollment and retention and be more inclusive of minority and lower health literacy participants.

Utility of the “2019 ACR/EULAR classification criteria” for the management of patients with IgG4-related disease

BackgroundThe 2019 ACR/EULAR Classification Criteria for IgG4-related disease (IgG4-RD) represent a fundamental tool for patient enrollment in research studies and in clinical trials but their usefulness in daily clinical practice remains unknown. ObjectiveTo validate the 2019 ACR/EULAR Classification Criteria for IgG4-RD in a real-life setting and to anticipate their utility for orienting disease diagnosis and patient management. MethodsFour experts were asked to classify 200 patients diagnosed with IgG4-RD according to the 2019 ACR/EULAR Classification Criteria for IgG4-RD. Agreement between experts was calculated and the Classification score of each patient was correlated with the following variables and outcomes: serum IgG4 and IgE; inflammatory markers; eosinophils; plasmablasts; IgG4-RD responder index; diabetes, osteoporosis, relapses; and use of rituximab. ResultsAmong the 157/200 cases equally rated by at least three experts, 94 (59.9%) achieved IgG4-RD classification and 63 (40.1%) did not. Strong agreement among IgG4-RD experts was observed in classifying patients (k = 0.711, p<0.0001). Clinical presentations not included in the classification algorithm and lack of informative histology were the most common reasons for not achieving classification. In patients achieving classification, the Classification score did not correlate with variables of disease activity and was not associated with specific outcomes. ConclusionsThe ACR/EULAR Classification Criteria represent a replicable instrument for classifying patients and a useful framework for orienting diagnosis but are of limited utility for assessing IgG4-RD activity, for predicting disease outcomes, and for defining personalized therapeutic approaches.

88 Racial and Gender Disparities Among Obese Patients With Pancreatic Cancer: A Trend Analysis From 2004–2018 in the United States

INTRODUCTION: Obesity increases the risk of pancreatic cancer by up to 50%. Epidemiologic studies indicate that disparities exist in obesity trends across different demographics in the United States. This is suspected to be from modifiable risk factors, comorbidities, and differences in the gut microbiome, along with social determinants of health such as a lack of access to high-volume treatment centers. Our aim is to determine if variation exists in the demographic of obese pancreatic cancer patients over the last 15 years. METHODS: We performed a retrospective analysis in the IBM Explorys database (1999–2018), a pooled, de-identified clinical database of unique patient records from 26 health care networks and 300 hospitals across the United States. At the time of analysis there were 63,744,040 patients, of which 9,620 were adults (&gt;18 years old) with both pancreatic cancer and obesity (BMI &gt;30). Patient populations were identified using SNOMED and ICD codes. Cochrane-Armitage testing was performed to analyze trends in obesity among pancreatic cancer patients between 2004–2018. Subgroup analysis for gender, age, race, and mortality rate were assessed. RESULTS: The percentage of obese patients with pancreatic cancer increased over the 15-year period (2.5% to 8.5%); P = &lt;0.0001). Rates of obesity among pancreatic cancer patients increased among females (P = 0.0004), individuals under age 65 years (P = 0.0002), and all-races, but especially for African Americans (P = 0.0007) and those in minority groups. CONCLUSION: Pancreatic cancer is becoming more common among patients who are obese, younger, female, and not Caucasian. African Americans have been shown to have a higher incidence and mortality from pancreatic cancer. This disparity has been attributed to lifestyle habits, co-morbidities including obesity, and a lack of access to high-volume treatment centers. However, differences in gene expression also increase the risk. Although these could be therapeutic targets, low minority enrollment in research studies is a barrier to progress. This is the first study to assess demographic trends in obese pancreatic cancer patients over the last 15 years. Awareness of disparities in pancreatic cancer and applying more precise population approaches to those at increased risk are essential to improving future outcomes. An integrated approach should include increased health care access and recruitment in research studies for minority groups.

Understanding Pre-Type 1 Diabetes: The Key to Prevention.

While the incidence of type 1 diabetes continues to rise by 3% each year, the ability to prevent this disease remains elusive. Hybrid closed loop devices, artificial pancreas systems, and continuous glucose monitoring technology have helped to ease the daily burden for many people living with type 1 diabetes. However, the artificial pancreas is not a cure; more research is needed to achieve our ultimate goal of preventing type 1 diabetes. The preceding decades have generated a wealth of information regarding the natural history of pre-type 1 diabetes. Islet autoimmunity in the form of multiple autoantibodies is known to be highly predictive of progression to disease. Staging systems have been devised to better characterize pre-type 1, direct mechanistic understanding of disease, and guide the design of prevention studies. However, there are no evidence-based recommendations for practitioners caring for autoantibody patients other than to encourage enrollment in research studies. Close monitoring of high-risk patients in natural history studies markedly reduces diabetic ketoacidosis rates at diagnosis and research participation is critical to finding a means of preventing type 1 diabetes. The discovery of an effective preventative strategy for type 1 diabetes will justify universal risk screening for all children.

Revised 'Common Rule' Shapes Protections For Research Participants.

Investigators and institutions have begun to prepare for new federal protections of study participants set to take effect in 2018.

Exploring the influence of demographic and medical characteristics of African-American and Latinas on enrollment in a behavioral intervention study for breast cancer survivors.

To better understand research participation among hard-to-reach populations, this exploratory investigation examined characteristics of enrollees and non-enrollees from a population-based longitudinal study with African-American and Latina-American breast cancer survivors. A mixed-method recruitment approach was utilized to enroll participants from cancer registries and community groups who were 1-6 years post-diagnosis. Four hundred and sixty-eight participants agreed to participate constituting an 81% participation rate; 65 and 55% completed Time-1, and both Time-1 and Time-2 assessments, respectively. African-Americans were more likely to agree to participate and complete the T1 assessment (73%) than Latinas (62%) (p < 0.05). Participation was influenced by educational attainment and comorbidities (p < 0.05) for African-Americans. Among Latinas, language proficiency, comorbidities and psychological difficulties (p < 0.01) influenced participation. Our findings suggest that enrollment in research studies may be influenced by complex and multi-dimensional factors stemming from subjects' characteristics including ethnicity, culture, language proficiency and literary, and socioeconomic status, as well as medical characteristics including co-occurring chronic illness and psychological status. Thus, comprehensive, multi-method research studies are urgently needed to better understand and address the challenge of minority recruitment in biomedical research. To increase research participation among cancer survivors, it is imperative to implement focused strategies that will support and encourage individuals' enrollment and continued participation in studies.

Challenges and Successes in Recruiting Firefighters for Hearing Loss Prevention Research

Noise-induced hearing loss (NIHL) is a significant occupational health problem in the United States, affecting more than 1 million firefighters. Noise hazards include vehicles, sirens, and power tools. Additionally, firefighters are commonly exposed to ototoxic chemicals. Because the use of hearing protection is not universally required for firefighters, firefighters must be educated about NIHL to ensure they take personal responsibility for hearing loss prevention. This study discusses challenges associated with recruiting firefighters to participate in a randomized, controlled trial testing a web-based hearing protection training program. Successful recruitment strategies included collaboration with key stakeholders, a flexible and convenient computer-based intervention, expansion to multiple recruitment sites, and interactive outreach to potential participants. Future research should use quantitative methods to evaluate and compare the effectiveness of specific recruitment strategies to facilitate firefighter enrollment in research studies. Developing and testing effective hearing protection interventions for firefighters is a crucial first step toward preventing NIHL in this population.

Certificates of Confidentiality and the Marshfield Clinic's Personalized Medicine Research Project

Enrollment in research studies is often limited by the fear that one’s personal information cannot be kept private. One way researchers can address this is by obtaining a certificate of confidentiality (CoC) for their study. This article briefly reviews what a certificate of confidentiality is, how to obtain one, and the Marshfield Clinic’s experience in recruiting for the Personalized Medicine Research Project.

Depression in amyotrophic lateral sclerosis

Depression is an under-recognized comorbidity associated with amyotrophic lateral sclerosis (ALS). The goals of this study were to prospectively estimate the prevalence of depression and other ALS related symptoms and to study the impact of depression on enrollment in research studies. One hundred and twenty-seven people with ALS completed the ALS Depression Inventory (ADI-12) and answered questions about ALS related symptoms and research study enrollment preferences. Demographics, ALS symptoms, medications, functional status, and research enrollment were compared between depressed and non-depressed patients. Results showed that the prevalence of mild and severe depression was 29% and 6%, respectively. More than one-third of our ALS patients were receiving anti-depressants to treat depression, sialorrhea, and pseudobulbar affect. Depression prevalence was not correlated with disease duration or progression. Except for anxiety, none of the ALS related symptoms predicted depression. The presence of depression did not have an effect on the decision to enroll in research studies. In conclusion, major depression is less common in our ALS cohort than in the general population. The diagnosis of depression can be masked by some ALS related symptoms and it has no impact on enrollment in ALS clinical trials.

Recruiting Vulnerable Populations into Research: A Systematic Review of Recruitment Interventions

Members of vulnerable populations are underrepresented in research studies. To evaluate and synthesize the evidence regarding interventions to enhance enrollment of vulnerable populations into health research studies. Studies were identified by searching MEDLINE, the Web of Science database, personal sources, hand searching of related journals, and article references. Studies that contained data on recruitment interventions for vulnerable populations (minority, underserved, poor, rural, urban, or inner city) and for which the parent study (study for which recruitment was taking place) was an intervention study were included. A total of 2,648 study titles were screened and 48 articles met inclusion criteria, representing 56 parent studies. Two investigators extracted data from each study. African Americans were the most frequently targeted population (82% of the studies), while 46% targeted Hispanics/Latinos. Many studies assessed 2 or more interventions, including social marketing (82% of studies), community outreach (80%), health system recruitment (52%), and referrals (28%). The methodologic rigor varied substantially. Only 40 studies (71%) incorporated a control group and 21% used statistical analysis to compare interventions. Social marketing, health system, and referral recruitment were each found to be the most successful intervention about 35-45% of the studies in which they were attempted, while community outreach was the most successful intervention in only 2 of 16 studies (13%) in which it was employed. People contacted as a result of social marketing were no less likely to enroll than people contacted through other mechanisms. Further work with greater methodologic rigor is needed to identify evidence-based strategies for increasing minority enrollment in research studies; community outreach, as an isolated strategy, may be less successful than other strategies.