Participation In Clinical Trials Research Articles

Characterization of Human Senescent Cell Biomarkers for Clinical Trials.

There is an increasing need for biomarkers of senescent cell burden to facilitate the selection of participants for clinical trials. p16Ink4a is encoded by the CDKN2A locus, which produces five variant transcripts in humans, two of which encode homologous p16 proteins: p16Inka4a, encoded by p16_variant 1, and p16ɣ, encoded by p16_variant 5. While distinct quantitative polymerase chain reaction primers can be designed for p16_variant 5, primers for p16_variant 1 also measure p16_variant 5 (p16_variant 1 + 5). In a recent clinical trial evaluating the effects of the senolytic combination, dasatinib + quercetin (D + Q), on bone metabolism in postmenopausal women, we found that women in the highest tertile for T-cell expression of p16_variant 5 had the most robust skeletal responses to D + Q. Importantly, the assessment of p16_variant 5 was more predictive of these responses than p16_variant 1 + 5. Here, we demonstrate that invitro, p16_variant 1 + 5 increased rapidly (Week 1) following the induction of DNA damage, whereas p16_variant 5 increased later (Week 4), suggesting that p16_variant 5 becomes detectable only when the abundance of senescent cells reaches some threshold. Further analysis identified a SASP panel in plasma that performed as well in identifying postmenopausal women with a positive skeletal response to D + Q. Collectively, our findings provide further support for the T-cell p16_variant 5 assay as a biomarker for selecting participants in clinical trials of senolytic interventions. In addition, our data indicate that correlated plasma SASP markers could be used in lieu of the more technically challenging T-cell p16 assay. Trial Registration: ClinicalTrials.gov identifier: NCT04313634.

“We don’t Get Drugs Targeted for Us:” Applying the Integrated Behavioral Model to Understand Why Black Women Chose to Participate in a Breast Cancer Clinical Trial

ABSTRACT Guided by the integrated behavioral model, the authors interviewed 14 Black breast cancer survivors (N = 14) who had participated in a breast cancer clinical trial. This study aimed to better understand what may motivate Black women to engage in medical research and decide to participate in medical research. Findings revealed that Black women’s altruistic desires to serve others and their communities are greatly influenced by the need to leave a “legacy” of better treatment for other Black women. The participants mostly learned about clinical trials through communicating with friends, family, or other breast cancer patients and survivors, rather than from their physicians. Many were influenced to participate by other Black breast cancer patients they knew, suggesting that social norms messaging may help alert other Black women about the continuing disparity in clinical trial participation. Finally, the participants in this study demonstrated high levels of involvement not only in seeking out clinical trials, but also in engaging in informed and shared decision-making with their providers about participating in the trials. The findings from this work illuminate important reasons Black women chose to participate in breast cancer clinical trials. Additionally, we offer robust and valuable theoretical and practical implications for researchers, so they can work toward successfully increasing Black women’s participation in clinical trials.

Assessing Experiences With Trofinetide for Rett Syndrome: Interviews With Caregivers of Participants in Clinical Trials.

Rett syndrome (RTT) is a rare neurodevelopmental disorder that mainly affects girls and women. Trofinetide is approved for the treatment of RTT in adults and children aged ≥2 years. To gain insight into experiences with RTT and effects of trofinetide treatment at different stages of RTT, interviews with caregivers of individuals with RTT were conducted upon their exit from the open-label trofinetide trials. Interviews were conducted with caregivers of participants in the LILAC/LILAC-2 open-label extension trials of the phase 3 LAVENDER trial in participants aged 5 to 20 years, and in DAFFODIL, an open-label trial in participants aged 2 to 4 years. Caregivers were asked about the RTT effects, experiences with trofinetide, meaningfulness of treatment effects, and satisfaction. Qualitative thematic analysis was performed. Caregivers of 33 participants from the open-label trials were interviewed, including 26 from LILAC/LILAC-2 (mean age, 12.3 years) and 7 from DAFFODIL (mean age, 4.5 years). The most commonly reported effects of RTT in LILAC/LILAC-2 were no verbal communication (24/26 [92.3%]), unable to use hands (15/26 [57.7%]), repetitive hand movements (15/26 [57.7%]), unable to walk (15/26 [57.7%]), and seizures (14/26 [53.8%]). In DAFFODIL, the most commonly reported effects of RTT were no verbal communication (7/7 [100%]), impaired balance (4/7 [57.1%]), unable to use hands (3/7 [42.9%]), repetitive hand movements (3/7 [42.9%]), mood disturbance (3/7 [42.9%]), constipation (3/7 [42.9%]), and limited ability to use hands (3/7 [42.9%]). Caregivers most commonly reported improvements in hand use (11/26 [42.3%]), engagement with others (11/26 [42.3%]), eye gaze (8/26 [30.8%]), use of the Tobii eye tracking device (7/26 [26.9%]), and attention/focus/concentration (7/26 [26.9%]) in LILAC/LILAC-2. In DAFFODIL, caregivers reported improvements in new words (5/7 [71.4%]), hand use (4/7 [57.1%]), and eye contact (4/7 [57.1%]). Nearly all (31/32) caregivers were very satisfied or satisfied with trofinetide. Caregivers of participants in open-label trofinetide trials reported improvements in RTT with meaningful impact in areas of motor function, communication, and engagement.

Digital Mammography, Tomosynthesis, and Contrast-Enhanced Mammography: Intraindividual Comparison of Mean Glandular Dose for Screening Examinations.

Background: Contrast-enhanced mammography (CEM) is growing in clinical use due to its increased sensitivity and specificity compared to full-field digital mammography (FFDM) and/or digital breast tomosynthesis (DBT), particularly in patients with dense breasts. Objective: To perform an intraindividual comparison of MGD between FFDM, DBT, a combination protocol using both FFDM and DBT (combined FFDM-DBT), and CEM, in patients undergoing breast cancer screening. Methods: This retrospective study included 389 women (median age, 57.4 years) at elevated risk of breast cancer who, as part of participation in an earlier prospective clinical trial, underwent breast cancer screening by combined FFDM-DBT and CEM between February 2019 and April 2021. A total of 764 breasts (383 left, 381 right) were evaluated. One craniocaudal (CC) view and one mediolateral oblique (MLO) view were evaluated per breast for each of FFDM, DBT, and CEM. MGD values were extracted from DICOM metadata. BI-RADS breast density categories were extracted from clinical radiology reports. Data were summarized descriptively, including determination of corresponding effective doses. Results: Breast density category was A in no patients, B in 44 patients (88 breasts), C in 306 patients (599 breasts), and D in 39 patients (77 breasts). Median MGD per breast (CC and MLO views combined) was 4.07 mGy for FFDM alone, 4.97 mGy for DBT alone, 9.38 mGy for combined FFDM-DBT, 3.96 mGy for low-energy CEM, 1.90 mGy for high-energy CEM, and 5.87 for CEM overall. Corresponding effective dose values were 0.49 mSv, 0.60 mSv, 1.13 mSv, 0.48 mSv, 0.23 mSv, and 0.70 mSv, respectively. Median MGD for density categories B, C, and D was 4.01 mGy, 4.22 mGy, and 2.70 mGy for FFDM; 5.93 mGy, 4.93 mGy, and 3.17 mGy for DBT; and 5.90 mGy, 6.02 mGy, and 4.52 mGy for CEM. Conclusion: In this intraindividual comparative study of screening examinations, MGD per breast was higher for CEM than for FFDM or DBT alone. However, these differences were small, and MGD was lower for CEM than for combined FFDM-DBT. Clinical Impact: These findings are relevant to ongoing considerations of the role of CEM in breast cancer screening pathways.

Motivation to Clinical Trial Participation: Health Information Distrust and Healthcare Access as Explanatory Variables and Gender as Moderator

Background: There is significant underrepresentation in clinical trials across diverse populations. Less is known about how health system-related factors, such as relationships and trust, mediate the motivation for clinical trial participation. We aimed to investigate whether health system-related factors explain the association between sociodemographic factors and motivation for participation. Additionally, we explored whether the mediating effects differ by gender. Methods: We used the Health Information National Trends Survey 2020 cycle-4 data. Motivation for clinical trial participation, assessed through eight items, was the outcome variable (range 1–4). Predictors included age, race, ethnicity, education, general health, and depression. The health system-related explanatory variables were health information distrust, having a regular provider, and the frequency of healthcare visits. Gender was the moderator. A structural equation model (SEM) was used for the overall and gender-stratified analyses. Results: Among the 3865 participants (mean [SE] age of 48.4 [0.53] years, 51.4% women, and 24.3% non-White), older age (β = −0.170; p < 0.001) and non-White race (β = −0.078; p < 0.01) were negatively associated, and higher education (β = 0.117; p < 0.001) was positively associated with motivation. Higher distrust (β = −0.094; p < 0.01) decreased motivation, whereas having a regular provider increased motivation (β = 0.087; p < 0.01). The gender-stratified SEM revealed that women, but not men, with higher distrust showed lower motivation (β = −0.121; p < 0.01), and men, but not women, with a regular healthcare provider showed higher motivation (β = 0.116; p < 0.01). Conclusions: Our study found that women with higher distrust showed lower motivation, while men with a regular healthcare provider demonstrated higher motivation. These gender differences highlight the need for tailored recruitment approaches that account for their distinct relationships with the health system.

Racial differences in clinical trial perceptions among a large, predominantly Black cohort of people with systemic lupus erythematosus in the Southeastern USA

ObjectiveBlack people in the USA have a higher incidence and severity of SLE and worse outcomes, yet they are significantly under-represented in SLE clinical trials. We assessed racial differences in...

Population encoding of observed and actual somatosensations in the human posterior parietal cortex

Cognition relies on transforming sensory inputs into a generalizable understanding of the world. Mirror neurons have been proposed to underlie this process, mapping visual representations of others' actions and sensations onto neurons that mediate our own, providing a conduit for understanding. However, this theory has limitations. Here, we hypothesize that mirror-like responses represent one facet of a broader framework in which our brains engage internal models for cognition. We recorded populations of single neurons in the human posterior parietal cortex (PPC) of a brain-machine interface clinical trial participant implanted with a microelectrode array while she either experienced actual touch, or observed diverse tactile stimuli applied to other individuals. Two body locations were tested, on each of the participant and other individuals. Some neurons exhibited mirror-like properties, consistent with earlier literature. However, they were fragile, breaking with increased task complexity. Population responses were better characterized by generalizable and compositional basic-level features encoded within neural subspaces. These features enable the population to respond to diverse actual and observed touch stimuli and are recruited similarly for similar forms of touch. Mirror-like neurons belong within these subspaces, contributing more globally to compositionality and generalizability. We speculate that at a population-level, human PPC manifests an internal model for touch, and that cognition unfolds in the high-level human cortex by versatility in its representational building blocks. In a broad sense, we speculate that the population features we demonstrate support a broad mechanism by which the high-level human cortex enables understanding.

Consent to recontact for future research using linked primary healthcare data: Outcomes and general practice perceptions from the ATHENA COVID-19 study

Background: The ATHENA COVID-19 study was set up to recruit a cohort of patients with linked health information willing to be recontacted in future to participate in clinical trials and also to investigate the outcomes of people with COVID-19 in Queensland, Australia, using consent. This report describes how patients were recruited, their primary care data extracted, proportions consenting, outcomes of using the recontact method to recruit to a study, and experiences interacting with general practices requested to release the primary care data. Methods: Patients diagnosed with COVID-19 from 1 January 2020 to 31 December 2020 were systematically approached to gain consent to have their primary healthcare data extracted from their general practice into a Queensland Health database and linked to other datasets for ethically approved research. Patients were also asked to consent to allow future recontact to discuss participation in clinical trials and other research studies. Patients who consented to recontact were later approached to recruit to a long-COVID study. Patients’ general practices were contacted to export the patient files. All patient and general practice interactions were recorded. Outcome measures were proportions of patients consenting to data extraction and research, permission to recontact, proportions of general practices agreeing to participate. A thematic analysis was conducted to assess attitudes regarding export of healthcare data, and the proportions consenting to participate in the long-COVID study were also reported. Results: Of 1212 patients with COVID-19, contact details were available for 1155; 995 (86%) were successfully approached, and 842 (85%) reached a consent decision. Of those who reached a decision, 581 (69%), 615 (73%) and 629 (75%) patients consented to data extraction, recontact, and both, respectively. In all, 382 general practices were contacted, of whom 347 (91%) had an electronic medical record compatible for file export. Of these, 335 (88%) practices agreed to participate, and 12 (3%) declined. In total, 526 patient files were exported. The majority of general practices supported the study and accepted electronic patient consent as legitimate. For the long-COVID study, 376 (90%) of those patients recontacted agreed to have their contact details passed onto the long-COVID study team and 192 (53%) consented to take part in their study. Conclusion: This report describes how primary care data were successfully extracted using consent, and that the majority of patients approached gave permission for their healthcare information to be used for research and be recontacted. The consent-to-recontact concept demonstrated its effectiveness to recruit to new research studies. The majority of general practices were willing to export identifiable patient healthcare data for linkage provided consent had been obtained.

Post-Pandemic Obstacles of Clinical Trial Participation in COVID-19 Studies

Post-Pandemic Obstacles of Clinical Trial Participation in COVID-19 Studies

Physical Activity Correlates With Skeletal Muscle MRI Findings in Individuals With Duchenne Muscular Dystrophy

ABSTRACTIntroduction/AimsSkeletal muscle magnetic resonance imaging (MRI) is a validated noninvasive tool to assess Duchenne muscular dystrophy (DMD) progression. There is interest in finding DMD biomarkers that decrease the burden of clinical trial participation, such as wearable devices. Our aim was to evaluate the relationship between activity, via accelerometry, and skeletal muscle MRI, particularly T2 mapping.MethodsDMD children and young adults completed skeletal muscle MRI and were asked to wear an accelerometer on the dominant wrist for 7 days. MRI data included fat‐suppressed transverse relaxation time (T2) mapping of the calves and longitudinal relaxation time (T1) mapping. Activity was assessed as vector magnitudes (VMs) and fraction of time (FOT) in activity groups (sedentary 1 or 2, low 1 or 2, moderate‐to‐vigorous physical activity (MVPA)).ResultsParticipants (n = 22; median age 11.4 years, 41% ambulatory) wore the accelerometer for a median of 7 days. Longer T2 in multiple lower extremity muscles was negatively correlated with VMs per minute (tibialis posterior Spearman's rho = −0.68, p < 0.001), even when accounting for age, ambulatory status, or glucocorticoid use. Longer T2 of the tibialis posterior was positively correlated with FOT in sedentary 1 (rho = 0.49, p = 0.02) and negatively correlated with FOT in higher activity levels (low 1 (rho = −0.58, p = 0.004), low 2 (rho = −0.67, p = 0.002), MVPA (rho = −0.7, p < 0.001)).DiscussionIn individuals with DMD, longer T2 on skeletal muscle MRI of the calves moderately correlated with lower activity levels indicating the potential use of home accelerometry as a future clinical trial biomarker of skeletal muscle health and progression in DMD.

Advancing Equitable Participation in Pediatric Clinical Trials Through Cognitive Interviewing.

Advancing Equitable Participation in Pediatric Clinical Trials Through Cognitive Interviewing.

Early antiviral CD4+ and CD8+ T cells are associated with upper airway clearance of SARS-CoV-2.

T cells are involved in protective immunity against numerous viral infections. Data regarding functional roles of human T cells in SARS-CoV-2 (SARS2) viral clearance in primary COVID-19 are limited. To address this knowledge gap, we assessed samples for associations between SARS2 upper respiratory tract viral RNA levels and early virus-specific adaptive immune responses for 95 unvaccinated clinical trial participants with acute primary COVID-19 aged 18-86 years old, approximately half of whom were considered at high risk for progression to severe COVID-19. Functionality and magnitude of acute SARS2-specific CD4+ and CD8+ T cell responses were evaluated, in addition to antibody responses. Most individuals with acute COVID-19 developed SARS2-specific T cell responses within 6 days of COVID-19 symptom onset. Early CD4+ T cell and CD8+ T cell responses were polyfunctional, and both strongly associated with reduced upper respiratory tract SARS2 viral RNA, independent of neutralizing antibody titers. Overall, these findings provide evidence for protective roles for circulating SARS2-specific CD4+ and CD8+ T cells during acute COVID-19.

The Australian clinical trial landscape: Perceptions of rural, regional and remote health service capacity and capability

BackgroundAccess to clinical trials is limited for rural, regional and remote Australians, adding to the current health inequity between rural and metropolitan populations. The Australasian Teletrial Model was developed to bring clinical trials “closer to home”. In 2020, the Australian Teletrial Program was funded to expand and support the uptake of the model across six Australian states and territories. The aim of this study was to explore and describe the clinical trial landscape in Australia prior to the implementation of the Australian Teletrial Program with a particular focus on rural, regional and remote health services.MethodsThis qualitative study provides a descriptive exploration of the clinical trial landscape across rural, regional and remote Australia. Data were obtained from semi-structured interviews (n = 33) and one focus group (n = 5) involving clinical trial stakeholders between August 2022 and May 2023. Deductive then inductive thematic analysis used the broad topic areas of the interview schedule as a framework, as follows: education and training, workforce, equipment and services, clinical trial sites, participant recruitment and clinical trial approval process.ResultsThis study identified barriers that are generalizable to the Australian clinical trial landscape and those specific to the rural, regional and remote health service context. The main barriers to conducting clinical trials in rural, regional and remote areas were lack of investment and engagement on the part of health service executives, workforce limitations, inconsistent training, lack of physical infrastructure and competing clinical priorities. Despite these challenges, clinicians reported enthusiasm for conducting clinical trials, and opportunities were reported for these health services to partner with larger metropolitan/regional health services, regional universities and communities to support the growth of clinical trial capability and capacity.ConclusionsThe clinical trial landscape in Australian health services varies in terms of quality and availability of training, workforce capacity, executive support, site capability and approval processes. The Australian Teletrial Program has an immense opportunity to overcome some of the reported challenges by supporting capacity and capability building. Ultimately, however, sustainable reform to bring trials closer to home requires a collaborative approach that considers implementation strategies across all levels of the health service and government, alongside other initiatives.

From trials to practice: Immune checkpoint inhibitor therapy for melanoma patients in Norway.

Norway has one of the highest rates of cutaneous melanoma (CM) incidence and mortality globally. Immune checkpoint inhibitor (ICI) therapy for CM was introduced between 2014 and 2017 to improve treatment and patient prognosis, but knowledge about its clinical usage is limited. This study investigates patient's characteristics and treatment patterns in real-world practice compared to clinical trial results. All adult (≥18) CM patients treated with ICI therapy in Norway from 2014 to 2021 were included, utilizing high-coverage data from multiple national registries to describe patients' health, socioeconomic factors, and treatment management, stratified by first ICI therapy. We compared patient and tumour characteristics with findings from five randomized controlled trials (RCTs). Among 2,083 patients receiving ICI therapy, 975 (47%) received nivolumab as their first treatment in the metastatic setting. Patients on combination therapy were younger and had higher education and income levels compared to those on monotherapy. Overall, real-world patients were older and had a higher incidence of brain metastases than those in RCTs. Approximately, 1 in 5 patients would have been excluded from RCTs due to pre-existing autoimmune diseases. Targeted therapy was the most common secondary systemic treatment after first-line PD-1 inhibitors. This study details ICI therapy in Norway, highlighting differences between real-world ICI users and clinical trial participants, raising questions about the effectiveness of this treatment for patients not eligible for trials.

The Tumor Immune Microenvironment and Therapeutic Efficacy of Trastuzumab Deruxtecan in Gastric Cancer.

This biomarker study explored HER2 expression levels and immune cell characteristics that may affect response to T-DXd using tumor tissue samples collected from clinical trial participants. The results suggest that HER2 expression levels and tumor characteristics before the initiation of T-DXd may correlate with the efficacy of the drug.

The Global Kidney Patient Trials Network and the CAPTIVATE Platform Clinical Trial Design

Chronic kidney disease (CKD) is a global health priority affecting almost 1 billion people. New therapeutic options and clinical trial innovations such as adaptive platform trials provide an opportunity to efficiently test combination therapies. To describe the design and baseline results of the Global Kidney Patient Trials Network (GKPTN) and the design and structure of the global adaptive platform clinical trial Chronic Kidney Disease Adaptive Platform Trial Investigating Various Agents for Therapeutic Effect (CAPTIVATE) to find new therapeutic options and treatments for people with kidney disease. The GKPTN is a multicenter registry that started in May 2020 and is ongoing, while CAPTIVATE is a multicenter, multifactorial, phase 3, placebo-controlled adaptive platform randomized clinical trial that includes patients with CKD. The first participant was randomized in September 2024. The GKPTN recruits patients from kidney and endocrinology practices, and CAPTIVATE aims to recruit patients from GKPTN sites where possible. Both the GKPTN and CAPTIVATE recruit patients with nondialysis CKD. CAPTIVATE will test several investigational agents or combinations of agents, beginning with a mineralocorticoid receptor antagonist. The GKPTN monitors clinical characteristics, treatment, and outcomes to identify eligible clinical trial participants and provide a contemporary global picture of patients with CKD. The primary outcome of CAPTIVATE is to identify investigational agents or combinations of agents to reduce the rate of chronic estimated glomerular filtration rate (eGFR) decline. The default maximum sample size per treatment arm in each domain, based on bayesian simulations, is 500 participants, providing approximately 90% power to detect a clinically meaningful improvement of 2.6 mL/min/1.73 m2 in eGFR at the end of the 104-week study period. The GKPTN has enrolled 4334 patients across 119 sites in 8 countries (US, Australia, Argentina, China, Italy, Canada, Spain, and Japan). The mean (SD) participant age at enrollment was 64.5 (16.2) years, 2542 participants (58.7%) were female, and diabetic kidney disease was most frequently reported among patients for CKD etiology (1875 [43.3%]). Among the participants, the mean (SD) eGFR was 52.9 (29.3) mL/min/1.73 m2, and the median urinary albumin-to-creatinine ratio was 89 mg/g (coefficient of variation, 20-420 mg/g). In the GKPTN cohort, the mean eGFR decline was steeper among participants with a baseline eGFR of 60 mL/min/1.73 m2 or more (-2.29 [95% CI, -3.14 to -1.44]) compared with those with an eGFR of less than 60 mL/min/1.73 m2 (-1.16 [95% CI, -1.77 to -1.44]) and was progressively steeper in more severe albuminuria subgroups. The GKPTN registry and the CAPTIVATE trial have the potential to expand and optimize therapeutic options for people with CKD using an adaptive platform clinical trial design. ClinicalTrials.gov Identifiers: NCT04389827 and NCT06058585.

New Strategies for Enhancing Enrollment of Underrepresented Minorites in Lymphoma Clinical Trials.

New lymphoma treatments, including chimeric antigen receptor (CAR) T-cells, bispecific antibodies, and immune checkpoint inhibitors, have significantly improved patient outcomes. Despite these therapeutic advances, only 2%-3% of adult cancer patients participate in clinical trials. This participation is even lower among certain groups, including ethnic and racial minorities, individuals with low socioeconomic status, rural residents, older adults, and young adults. Under-representation of these groups in clinical trials limits the generalizability of trial results and is detrimental to those populations that do not receive equal access to novel therapies. Although racial and ethnic minorities constitute over 40% of the U.S. population, they make up only about 15% of clinical trial participants. The US FDA now requires sponsors seeking regulatory approval for therapies via registrational clinical trials to submit a plan to ensure diversity among trial participants. This article addresses Strategies for Enhancing Enrollment of Underrepresented Minorities in Lymphoma Clinical Trials.

Reasons for Declining Participation in Inpatient Research Among Historically Minoritized Racial and Ethnic Communities: A Scoping Review

BackgroundTo promote equitable recruitment for studies conducted in the inpatient hospital setting, we sought to characterize reasons why individuals, both from historically minoritized racial and ethnic groups and the broader patient population, refuse participation in clinical trials within inpatient settings. MethodsAn exhaustive search of the literature was conducted in Cochrane Library, Google Scholar, Embase, MEDLINE, PubMed, Scopus, and Web of Science databases to find relevant articles published from the inception of each database to April 30, 2023. Studies recruiting patients during their inpatient stay and reporting reasons for refusing participation in clinical trials met the inclusion criteria. ResultsThe search resulted in 2264 citations, of which 22 were included. 14 did not report data related to race, while 19 reported no ethnicity data. Reasons for refusal across trials included study burden and inconvenience (n=16), transportation and logistical issues (n=13), lack of interest in research (n=12), and refusal to be randomized (n=10). Prominent concepts included the importance of incorporating social support systems in consenting processes, lack of efforts to include data or recruitment efforts for individuals from minoritized groups, and physician involvement in recruitment. DiscussionTo enhance participation among historically minoritized communities in clinical trials, greater efforts must be made to collect demographic information and document refusal reasons to inform future recruitment methods. Strategies include proactively accounting for culture and language differences in study design and recruitment and intentionally engaging social support networks. Limiting study burden and logistics and optimizing collaborations between clinical and research teams would promote accessibility and foster patient trust.

Participation in Clinical Trials Does Not Have to Be a Lousy Experience.

Participation in Clinical Trials Does Not Have to Be a Lousy Experience.

Barriers and Facilitators to the Participation of Pregnant Women in Clinical Research: A Mixed-Methods Systematic Review.

Pregnant women had a large demand for diagnosis and treatment, but the clinical research was not sufficient, and there were many barriers for pregnant women to participate in clinical research. This study aimed to systematically identify these barriers and facilitators, map them with Theoretical Domains Framework (TDF) and Behavior Change Techniques (BCTs) to inform the development of interventions promoting pregnant women's involvement in clinical research. This was a mixed-methods systematic review. PubMed, Embase, Cochrane Library, APA PsycInfo, CINAHL, China National Knowledge Infrastructure, WanFang, VIP Database for Chinese Technical Periodicals, Chinese Biomedical Literature Database, and related references were searched. Qualitative, quantitative, and mixed-methods studies exploring barriers and facilitators to pregnant women's participation in clinical trials were included. The barriers and facilitators were extracted, after transforming the quantitative data into qualitative data, all qualitative data were used to thematic synthesis. The identified barriers and facilitators were mapped into TDF and BCTs. A total of 103 studies (66 qualitative, 24 quantitative, and 13 mixed-methods) were included. Three main themes were formed: personal factors, environmental factors and research characteristics, with identified barriers and facilitators within each theme. "Knowledge," "Environmental Context and Resources," and "Beliefs about Consequences" were the main domains where barriers and facilitators identified by pregnant women and researchers were mapped in TDF. Additionally, the barriers and facilitators identified by pregnant women also mapped on "Social Influences" and "Goals." "Instruction on how to perform a behavior," "restructuring the physical environment," "salience of consequences," "social support (unspecified)," "goal setting (outcome)" were the main BCTs identified based on barriers and facilitators. The barriers and facilitators to clinical research participation identified in this study involved three main themes of personal, environmental, and research characteristics, which mainly mapped to five TDF domains. Based on these barriers and facilitators, 23 BCTs were identified. Future research should focus on developing behavior change interventions, assessing their efficacy and implementability.