Impact of financial compensation on enrollment and participation in a remote, mobile-app based research study.

Background: There is no consensus on how to determine appropriate financial compensation for research recruitment. Selecting incentive amounts that are reasonable and respectful, without undue inducement, remains challenging. Previously, we demonstrated that incentive amount significantly impacts participants' willingness to complete various hypothetical research activities.

Repurposing N-acetylcysteine for management of non-acetaminophen induced acute liver failure: an evidence scan from a global health perspective.

Background: The World Health Organization (WHO)'s Essential Medicines List (EML) plays an important role in advocating for access to key treatments for conditions affecting people in all geographic settings. We applied our established drug repurposing methods to one EML agent, N-acetylcysteine (NAC), to identify additional uses of relevance to the global health community beyond its existing EML indication (acetaminophen toxicity).

Methods: We undertook a phenome-wide association study (PheWAS) of a variant in the glutathione synthetase () gene in approximately 35,000 patients to explore novel indications for use of NAC, which targets glutathione.

Taking AIM at serious illness: implementing an access to investigational medicines expanded access program.

When seriously ill patients have exhausted all treatment options available as part of usual care, the use of investigational agents may be warranted. Food and Drug Administration's (FDA) Expanded Access (EA) pathway provides a mechanism for these patient's physicians to pursue use of an investigational agent outside of a clinical trial when trial enrollment is not a feasible option. Though FDA has recently implemented processes to significantly streamline the regulatory portion of the process, the overall pathway has several time-consuming components including communication with the pharmaceutical company and the associated institutional requirements for EA use (contracting, Institutional Review Board [IRB], pharmacy, billing).

Walk before you run: Feasibility challenges and lessons learned from the PROCLAIM study, a multicenter randomized controlled trial of misoprostol for prevention of recurrent Clostridioides difficile during COVID-19.

We analyzed our challenging experience with a randomized controlled trial of misoprostol for prevention of recurrent C. difficile. Despite careful prescreening and thoughtful protocol modifications to facilitate enrollment, we closed the study early after enrolling just 7 participants over 3 years.

Recruitment and retention for chronic pain clinical trials: a narrative review.

Opioid misuse is at a crisis level. In response to this epidemic, the National Institutes of Health has funded $945 million in research through the Helping to End Addiction Long-term (HEAL) Pain Management Initiative, including funding to the Vanderbilt Recruitment Innovation Center (RIC) to strategize methods to catalyze participant recruitment. The RIC, recognizing the challenges presented to clinical researchers in recruiting individuals experiencing pain, conducted a review of evidence in the literature on successful participant recruitment methods for chronic pain trials, in preparation for supporting the HEAL Pain trials.

How do Hispanics/Latinos Perceive and Value the Return of Research Results?

Interest in the return of research results has been increasing; however, little is known about how Hispanics/Latinos perceive and value receiving results. This study examined differences among Hispanics/Latinos by education and income in the experience and expectations about the return of research results, perceived value of specific types of information, and the least and most valuable specific information. Retrospective observational design using a cross-sectional national survey sample of Hispanics/Latinos (n = 327).

The Recruitment Innovation Center: Developing novel, person-centered strategies for clinical trial recruitment and retention.

Clinical trials continue to face significant challenges in participant recruitment and retention. The Recruitment Innovation Center (RIC), part of the Trial Innovation Network (TIN), has been funded by the National Center for Advancing Translational Sciences of the National Institutes of Health to develop innovative strategies and technologies to enhance participant engagement in all stages of multicenter clinical trials. In collaboration with investigator teams and liaisons at Clinical and Translational Science Award institutions, the RIC is charged with the mission to design, field-test, and refine novel resources in the context of individual clinical trials.

Human and Machine Intelligence Together Drive Drug Repurposing in Rare Diseases.

Repurposing is an increasingly attractive method within the field of drug development for its efficiency at identifying new therapeutic opportunities among approved drugs at greatly reduced cost and time of more traditional methods. Repurposing has generated significant interest in the realm of rare disease treatment as an innovative strategy for finding ways to manage these complex conditions. The selection of which agents should be tested in which conditions is currently informed by both human and machine discovery, yet the appropriate balance between these approaches, including the role of artificial intelligence (AI), remains a significant topic of discussion in drug discovery for rare diseases and other conditions.

Engaging smokers in research: Utility of Facebook in facilitating recruitment to a smoking cessation study.

Introduction: Social media, including Facebook outreach, is increasingly being used as a participant recruitment tool, and may be particularly useful in tobacco and smoking cessation studies. The Recruitment Innovation Center at Vanderbilt University Medical Center partnered with Project LUNA, a smoking cessation study, to conduct a pilot social media campaign aimed at increasing study recruitment.

Methods: Two posts encouraging study participation were developed and promoted on Facebook to users with an interest in smoking-related topics, with a link to a study-specific webpage.

Opening doors to clinical trial participation among Hispanics: Lessons learned from the Spanish translation of ResearchMatch.

Introduction: Clinical trial participation among US Hispanics remains low, despite a significant effort by research institutions nationwide. ResearchMatch, a national online platform, has matched 113,372 individuals interested in participating in research with studies conducted by 8778 researchers. To increase accessibility to Spanish speakers, we translated the ResearchMatch platform into Spanish by implementing tenets of health literacy and respecting linguistic and cultural diversity across the US Hispanic population.

The Astounding Breadth of Health Disparity: Phenome-Wide Effects of Race on Disease Risk.

Objective: We conducted a phenotype-wide association study (PheWAS) to compare diagnoses among Blacks with those of Whites in one health center in Tennessee using data from 1,883,369 patients.

Methods: We used our deidentified EHR, the Synthetic Derivative, to assess risk of diagnoses associated with Black as compared with White race using Firth logistic regression with covariates including age, sex, and density of clinical encounters.

Results: There were anchoring associations in both directions, including the highest increased risk for Blacks of having sickle cell anemia, and strongest decreased risk of basal cell carcinoma.

Uncovering Outcome Disparities of β Adrenergic Agonists in Blacks: A Systematic Review.

Purpose: Outcome differences driven by variation in Blacks' biologic response to treatment may contribute to persistent racial disparities in asthma morbidity and mortality. This review assessed systematic variation in β agonist treatment outcomes among Blacks compared to other groups.

Methods: We conducted a systematic review of studies reporting differential response to β agonists among Blacks, including studies identifying pharmacogenetic variants.

Exploring Biologic Predictors Response Disparities to Atypical Antipsychotics among Blacks: A Quasi-Systematic Review.

Purpose: Management of schizophrenia among Blacks in the United States is affected by persistent disparities. This review explored response to atypical antipsychotics among Blacks compared with other groups to assess systematic variation that may contribute to disparities.

Methods: We conducted a quasi-systematic review of studies reporting response to atypical antipsychotics among Blacks compared with other groups, including effects of genetic variation.

Leveraging Human Genetics to Identify Safety Signals Prior to Drug Marketing Approval and Clinical Use.

Introduction: When a new drug or biologic product enters the market, its full spectrum of side effects is not yet fully understood, as use in the real world often uncovers nuances not suggested within the relatively narrow confines of preapproval preclinical and trial work.

Objective: We describe a new, phenome-wide association study (PheWAS)- and evidence-based approach for detection of potential adverse drug effects.

Methods: We leveraged our established platform, which integrates human genetic data with associated phenotypes in electronic health records from 29,722 patients of European ancestry, to identify gene-phenotype associations that may represent known safety issues.

Broad-scale informed consent: A survey of the CTSA landscape.

Introduction: Research opportunities associated with the proliferation of the electronic health record (EHR), big data initiatives, and innovative approaches to trial design can present challenges for obtaining and documenting informed consent. Broad-scale informed consent (a term used herein to describe institutional models, rather than the Common Rule's strict regulatory definition for "broad consent") may facilitate the use of existing data and samples and speed the pace of research by minimizing barriers to consent. We explored the use of broad-scale informed consent within the Clinical Translational Science Award (CTSA) Program Network.

To end disease tomorrow, begin with trials today: Digital strategies for increased awareness of a clinical trials finder.

Introduction: Individuals experiencing different medical conditions, as well as healthy volunteers, may often be interested in trial participation, and researchers similarly need to find participants to advance medical knowledge. The ResearchMatch (RM) Trials Today clinical trial searching tool leverages clinicaltrials.gov data to enable potential participants to look for trial opportunities relevant to their situation.

Using What We Already Have: Uncovering New Drug Repurposing Strategies in Existing Omics Data.

The promise of drug repurposing is to accelerate the translation of knowledge to treatment of human disease, bypassing common challenges associated with drug development to be more time- and cost-efficient. Repurposing has an increased chance of success due to the previous validation of drug safety and allows for the incorporation of omics. Hypothesis-generating omics processes inform drug repurposing decision-making methods on drug efficacy and toxicity.

COMPASS: A Pilot Trial of an Early Palliative Care Intervention for Patients With End-Stage Liver Disease.

Context: Palliative care interventions have shown promise in improving quality of life and reducing health-care utilization among patients with chronic organ failure.

Objectives: To evaluate the effect of a palliative care intervention for adults with end-stage liver disease.

Methods: A randomized controlled trial of patients with end-stage liver disease admitted to the hepatology service at a tertiary referral center whose attending hepatologist indicated they would not be surprised if the patient died in the following year on a standardized questionnaire was performed.

Development of the Initial Surveys for the All of Us Research Program.

Background: The All of Us Research Program is building a national longitudinal cohort and collecting data from multiple information sources (e.g., biospecimens, electronic health records, and mobile/wearable technologies) to advance precision medicine.

We're not all cut from the same cloth: TAILORing treatments for children with chronic conditions.

Background: Finding the optimal treatment for a chronic condition can be a complex and lengthy endeavor for both the patient and the clinician. To address this challenge, we developed an "N-of-1" quality improvement infrastructure to aid providers and patients in personalized treatment decision-making using systematic assessment of patient-reported outcomes during routine care.

Methods: Using the REDCap data management infrastructure, we implemented three pediatric pilots of the Treatment Assessments in the Individual Leading to Optimal Regimens (TAILOR) tool, including children receiving early intervention, children with attention deficit hyperactivity disorder, and children with challenging behaviors in the classroom setting.

Understanding What Information Is Valued By Research Participants, And Why.

There is growing public demand that research participants receive all of their results, regardless of whether clinical action is indicated. Instead of the standard practice of returning only actionable results, we propose a reconceptualization called "return of value" to encompass the varied ways in which research participants value specific results and more general information they receive beyond actionable results. Our proposal is supported by a national survey of a diverse sample, which found that receiving research results would be valuable to most (78.

Connecting the public with clinical trial options: The ResearchMatch Trials Today tool.

Potential participants seek information about clinical trials for many reasons, but the process can be challenging. We analyzed 101,249 searches in ResearchMatch Trials Today, a free interface to recruiting trials from ClinicalTrials.gov.

A Phenome-Wide Association Study Uncovers a Pathological Role of Coagulation Factor X during Infection.

Coagulation and inflammation are interconnected, suggesting that coagulation plays a key role in the inflammatory response to pathogens. A phenome-wide association study (PheWAS) was used to identify clinical phenotypes of patients with a polymorphism in coagulation factor X. Patients with this single nucleotide polymorphism (SNP) were more likely to be hospitalized with hemostatic and infection-related disorders, suggesting that factor X contributes to the immune response to infection.

Patient and healthcare provider views on a patient-reported outcomes portal.

Background: Over the past decade, public interest in managing health-related information for personal understanding and self-improvement has rapidly expanded. This study explored aspects of how patient-provided health information could be obtained through an electronic portal and presented to inform and engage patients while also providing information for healthcare providers.

Methods: We invited participants using ResearchMatch from 2 cohorts: (1) self-reported healthy volunteers (no medical conditions) and (2) individuals with a self-reported diagnosis of anxiety and/or depression.