Participation In Clinical Studies Research Articles

228. Infection Control Cluster Randomized Control Trials and Healthcare Facility Participation: A Need for Readiness Assessment

Abstract Background Validated tools to evaluate organizational readiness exist within the implementation science literature, but readiness assessments for healthcare organization participation in cluster randomized control trials (CRCTs) have not been developed. CRCTs have been important for increasing the evidence base for infection control. This study describes complex contextual factors that can impact participation in a multi-site infection control CRCTs within the VA healthcare system. Methods To assess study participation eligibility and feasibility, a survey of ten inpatient acute care patient units within five VA healthcare facilities was conducted to evaluate standard eligibility criteria such as facility and patient unit demographics, infection rates, and letters of support from leadership. With study delays we began conducting readiness evaluations through email communications and conference calls. We identified several metrics of readiness including competing priorities, identification of champions/ stakeholder engagement, and research infrastructure. Results Our Initial survey metrics received from facilities interested in study participation were efficient in detecting study eligibility but lacked efficiency to detect study feasibility. Later metrics identified barriers to feasible study implementation (i.e., readiness), primarily competing priorities, specifically due to the pandemic. Other barriers included the lack of research infrastructure and lack of champion identification/stakeholder engagement. These contextual factors were generally elicited through ongoing communication rather than from the initial survey assessment. Conclusion Organizational readiness can delay or impede important infection control CRCTs. This study exemplifies the complexity of healthcare organizations participation in clinical studies that may not be addressed in existing readiness tools or assessments. The emergence of the covid pandemic amplified the importance of identifying a wide range of contextual factors that need to be captured in ongoing assessments for readiness. An essential first step in developing organizational readiness tools and assessments is to identify and define readiness constructs in complex changing healthcare settings. Disclosures All Authors: No reported disclosures.

A Bayesian method for safety signal detection in ongoing blinded randomised controlled trials.

Sponsors have a responsibility to minimise risk to participants in clinical studies through safety monitoring. The FDA Final Rule for IND Safety Reporting requires routine aggregate safety evaluation, including in ongoing blinded studies. We are interested in estimating the probability that the true adverse event rate in the experimental arm exceeds that in the control arm. We developed a Bayesian approach that specifies an informative meta-analytic predictive prior on the event probability in the control arm and an uninformative prior on that in the experimental arm. We combined these priors with a mixture likelihood that considers each patient in the ongoing blinded study may belong to the experimental or control arm. This allowed us to estimate the quantity of interest without unblinding. We evaluated our method by simulation, pairing scenarios that differed only in whether a safety signal was present or missing, and quantifying the ability of our model to discriminate using signal detection theory. Our approach shows benefit. It detects safety signals more reliably with greater sample sizes and for common rather than rare events. Performance does not deteriorate markedly when historical studies exhibit heterogeneous hazards or non-constant hazards. Our method will allow us to monitor safety signals in ongoing blinded studies with the goal of earlier identification and risk mitigation. Our method could be adapted to use informative priors on both arms or predictive covariates where pertinent data exist. We stress that ongoing safety monitoring should involve a multi-disciplinary team where statistical methods are paired with medical judgement.

INVESTIGATING THE EFFECT OF INSPIRED OXYGEN FRACTION ON RIGHT VENTRICULAR 3D STRAIN DURING GENERAL ANAESTHESIA IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE.

<h3>Introduction</h3> Patients with coronary artery disease (CAD) undergoing general anesthesia are at risk of perioperative complications. Hyperoxia is a known coronary vasoconstrictor. However, it is also a pulmonary vasodilator, reducing right ventricular afterload. Thus, there may be competing effects of hyperoxia on right ventricular function. In this study we investigated the effects of hyperoxia and normoxia on right ventricular (RV) function assessed by 3D transesophageal echocardiography (TEE) during general anesthesia in CAD patients before elective coronary artery bypass graft surgery. <h3>Methods</h3> In this randomized clinical trial study participants (n=106) were prospectively recruited using a crossover design. In anesthetized patients the fraction of inspired oxygen (FiO2) was titrated to a normoxic state (FiO2=0.3) and a hyperoxic state (FiO2=0.8). At both states TEE images were acquired to assess RV ejection fraction (RVEF) and global longitudinal free-wall strain (RVGLS). <h3>Results</h3> There was no difference between normoxia and hyperoxia in RVEF (46±6% vs. 45±8, p=0.504) nor in RVGLS (-22.4±4.8 vs. -21.9±4.3, p=0.352). However, RV function improved and worsened in some patients. ROC analysis (Figure A) shows that RVGLS at normoxia can better predict, which patients will worsen with excess oxygen. With a cut-off of -20% for RVGLS (Sensitivity: 87%, Specificity: 49%), it was demonstrated that hyperoxia was beneficial for patients with a poor strain at normoxia (>-20%) but detrimental for those with normal strain at normoxia (<-20%, Figure B), while RVEF with a cut-off of 40% (Sens: 88%, Spec: 33%) was unable to predict this response (Figure C.). <h3>Conclusion</h3> In CAD patients undergoing general anaesthesia, hyperoxia has heterogenous effects on the RV and the potential detrimental effects of hyperoxia were best predicted by RVGLS. Intraoperative strain analysis might be a tool to target oxygen levels based on individual needs.

Recruitment strategies for a post cessation weight management trial: A comparison of strategy cost-effectiveness and sample diversity

BackgroundEffective recruitment of representative and diverse samples in research trials is important to the generalizability of findings and in describing access to behavioral interventions. The current study evaluated the effectiveness of local and national recruitment strategies for a smoking cessation and weight management-focused randomized controlled trial (Fit & Quit). The overall cost-effectiveness of recruitment strategies was also evaluated. MethodsThe study initially recruited participants locally in the Memphis, TN area and later transitioned to national recruitment, necessitated by the transition to remote assessment strategies due to the COVID-19 pandemic. The study evaluated effective recruitment strategies for randomized participants (n = 305) across gender, race, rurality, and recruitment method, as well as the cost-effectiveness of methods used during the recruitment period of this study. ResultsThe most effective recruitment strategies were local postcards, local radio advertisements, word-of-mouth referrals, and national internet advertisements, which resulted in a combined 71.8% (n = 219) of the total randomized sample (n = 305). Radio advertisements were the best method for recruiting Black participants. Electronic recruitment strategies were the most effective method for non-urban participants. Additionally, gender, recruitment method, race, and rurality predicted randomization. Overall, electronic media methods were more cost-effective ($430.97 per participant) compared to traditional media methods ($931.43 per participant); however, traditional media methods resulted in a greater number of recruited and randomized participants. ConclusionResults provide information on effective and cost-effective local and national recruitment methods for recruiting underrepresented groups of participants in behavioral clinical intervention studies.

Inverse Salt Sensitivity of Blood Pressure Is Associated with an Increased Renin-Angiotensin System Activity.

High and low sodium diets are associated with increased blood pressure and cardiovascular morbidity and mortality. The paradoxical response of elevated BP in low salt diets, aka inverse salt sensitivity (ISS), is an understudied vulnerable 11% of the adult population with yet undiscovered etiology. A linear relationship between the number of single nucleotide polymorphisms (SNPs) in the dopamine D2 receptor (DRD2, rs6276 and 6277), and the sodium myo-inositol cotransporter 2 (SLC5A11, rs11074656), as well as decreased expression of these two genes in urine-derived renal proximal tubule cells (uRPTCs) isolated from clinical study participants suggest involvement of these cells in ISS. Insight into this newly discovered paradoxical response to sodium is found by incubating cells in low sodium (LS) conditions that unveil cell physiologic differences that are then reversed by mir-485-5p miRNA blocker transfection and bypassing the genetic defect by DRD2 re-expression. The renin-angiotensin system (RAS) is an important counter-regulatory mechanism to prevent hyponatremia under LS conditions. Oversensitive RAS under LS conditions could partially explain the increased mortality in ISS. Angiotensin-II (AngII, 10 nmol/L) increased sodium transport in uRPTCs to a greater extent in individuals with ISS than SR. Downstream signaling of AngII is verified by identifying lowered expression of nuclear factor erythroid 2-related factor 2 (NRF2), CCCTC-binding factor (CTCF), and manganese-dependent mitochondrial superoxide dismutase (SOD2) only in ISS-derived uRPTCs and not SR-derived uRPTCs when incubated in LS conditions. We conclude that DRD2 and SLC5A11 variants in ISS may cause an increased low sodium sensitivity to AngII and renal sodium reabsorption which can contribute to inverse salt-sensitive hypertension.

The COVID-19 pandemic as a catalyst for innovation: a regulatory framework to assess fit-for-purpose innovative approaches in clinical research

The COVID-19 pandemic has had a devastating impact on individuals and multiple aspects of our society including healthcare and clinical research. The silver lining is that the pandemic also served as a catalyst for wider adoption of innovative approaches in clinical research, notably the use of mobile or remote services, and digital technologies. Regulators, clinical study investigators, clinical study participants, sponsors, and other stakeholders collaborated to adopt measures that ensured safe participation in clinical studies whilst maintaining study integrity. In this article, we propose a regulatory framework for assessing fit-for-purpose innovative approaches in clinical research based on Roche/Genentech’s experience during the COVID-19 pandemic with the aim to inform and encourage broader implementation of patient-centric and sustainable innovation in clinical research. Our goal is to contribute to ongoing discussions on introducing innovative approaches in clinical trials and eventually the development of globally harmonised guidelines.

Measurement of Saccade Parameters in Relation to Adaptation to Homonymous Hemianopia.

Purpose:To report saccade parameters in participants during adaptation to post-stroke homonymous hemianopia.Methods:In a prospective observational case cohort study, adult stroke survivors with new onset homonymous hemianopia were recruited. Using quantitative measurement, saccade parameters were measured and compared between the hemianopic and non-hemianopic sides. Two participants with longitudinal measurements were compared with age-matched controls.Results:Of 144 clinical study participants, quantitative saccade measurements were only possible in 14 due to an inability to visualise targets on the hemianopic side in the majority. In 9 of the 14 participants, at four weeks post-stroke, mean (±SD) saccade latency was significantly longer to the hemianopic (328.4 ± 105.9 ms) compared to the non-hemianopic side (234.7 ± SD53.6 ms; t = 4.2, df = 8, p = 0.003). The number of correct saccadic responses out of 50 was significantly lower to the hemianopic side (36.6 ± SD14.1) in comparison to the non-hemianopic side (44.4 ± SD7.5; t = –3.1, df = 8, p = 0.014). In two participants studied over an eight-week time period, saccadic differences to the hemianopic side persisted despite apparent recovery of visual field.Conclusion:As participants with residual visual field loss were unable to perform quantitative assessments, the widespread use of this approach in this setting is limited. However, in those whom measurements were possible, there were statistically significant differences in saccade parameters between hemianopic and non-hemianopic sides that persisted post-visual recovery. Exploration of saccades in relation to adaptation to hemianopia and response to saccadic scanning/search training requires further examination.

Race/ethnicity matching boosts enrollment of black participants in clinical trials

BackgroundEnrollment of a representative sample of racial or ethnic-minority participants can be challenging for researchers conducting clinical trials. One proposed solution is race/ethnicity matching (i.e., aligning the racial or ethnic identity of the trial recruiter with that of the desired participant), but in practice this idea has yielded mixed results. Nevertheless, the approach seems inherently strong, so we reevaluated this strategy in a secondary analysis. MethodsBlack participant enrollment was tracked during the screening phase of two clinical trials led by the same PI and conducted in the same setting: the NICU of a midwestern academic hospital in a predominantly White locale. In the first trial, the recruiter was a White neonatal nurse practitioner from the NICU. In the second trial, the recruiter was a Black research nurse. In this evaluation of race/ethnicity matching, the number of Black women who enrolled into the screening phase of the two trials was compared. ResultsThe Black research nurse enrolled twice as many Black participants into the screening phase of a clinical trial compared to the White NICU neonatal nurse practitioner (12.24% & 6.1%, respectively). The 6.14 percentage-point difference in Black participant enrollment is significant using Fisher's exact test (p = 0.035). ConclusionsThe key finding is that the Black recruiter enrolled a significantly greater number of Black participants than the White recruiter, suggesting that race/ethnicity matching is a viable strategy for increasing racial/ethnic minority participation in clinical studies.

Consensus on informed consent for participants in cancer clinical studies (2021 edition)

To fully protect the rights of participants in cancer clinical studies and clarify the key points for the ethics review of the content of informed consent forms and the process of collecting informed consent, the Medical Ethics Professional Committee of the China Anti-Cancer Association engaged in joint discussions with the ethics committees of well-known cancer hospitals in China to formulate this consensus, along with the attached general template for informed consent forms for cancer clinical studies. This work is expected to provide guidance and suggestions for the practice of the sponsors, researchers, and ethics committees.

Educational intervention for providers addressing the diversity gap in cervical cancer clinical study participation (579)

Objectives: Every year, over 570,000 women worldwide are diagnosed with cervical cancer. Cervical cancer accounts for 7.5% of female cancer deaths, and 85% of those deaths occur in low- to moderate-income countries. In the US, it is estimated that Black women have a 30% higher incidence of cervical cancer than White women. Additionally, Hispanic women are 40% more likely to be diagnosed with cervical cancer than non-Hispanic women. In 2020, the US Food and Drug Administration issued industry guidance for enhancing the diversity of clinical study participants, highlighting the critical need for representative studies that reflect the current US population demographics. This study aims to conduct an educational intervention aimed at cervical cancer investigators and patients to increase ethnocultural diversity in clinical study recruitment in a cervical cancer research program. Methods: This educational intervention implemented a pre-post study design of clinical investigators participating in both global Phase 2 and Phase 3 cervical cancer studies. The Phase 3 clinical study serves as the parent foundational study to the Phase 2 study (ongoing study, NCT04646005), as 77% of the clinical investigators participating in Phase 2 clinical study overlap with the Phase 3 study. The ongoing Phase 2 study will educate investigators on ethnocultural diversity, and the inclusion of the two studies will be compared from pre-intervention (Phase 3) to post-intervention (Phase 2). Education will be provided as a one-time virtual training and a supplementary pamphlet and will cover the incidence and mortality differences across races, current enrollment gaps, barriers to including diverse populations, and guidance for the broader inclusion of women in our sponsored studies. Race and ethnicity demographic data for the Phase 2 trial (post-intervention) will be compared with the Phase 3 trial (pre-intervention) using the chi-square statistical test. Assuming significant results, a Z-test will then be used to assess the proportions of each race and ethnicity group. Objectives: Every year, over 570,000 women worldwide are diagnosed with cervical cancer. Cervical cancer accounts for 7.5% of female cancer deaths, and 85% of those deaths occur in low- to moderate-income countries. In the US, it is estimated that Black women have a 30% higher incidence of cervical cancer than White women. Additionally, Hispanic women are 40% more likely to be diagnosed with cervical cancer than non-Hispanic women. In 2020, the US Food and Drug Administration issued industry guidance for enhancing the diversity of clinical study participants, highlighting the critical need for representative studies that reflect the current US population demographics. This study aims to conduct an educational intervention aimed at cervical cancer investigators and patients to increase ethnocultural diversity in clinical study recruitment in a cervical cancer research program. Methods: This educational intervention implemented a pre-post study design of clinical investigators participating in both global Phase 2 and Phase 3 cervical cancer studies. The Phase 3 clinical study serves as the parent foundational study to the Phase 2 study (ongoing study, NCT04646005), as 77% of the clinical investigators participating in Phase 2 clinical study overlap with the Phase 3 study. The ongoing Phase 2 study will educate investigators on ethnocultural diversity, and the inclusion of the two studies will be compared from pre-intervention (Phase 3) to post-intervention (Phase 2). Education will be provided as a one-time virtual training and a supplementary pamphlet and will cover the incidence and mortality differences across races, current enrollment gaps, barriers to including diverse populations, and guidance for the broader inclusion of women in our sponsored studies. Race and ethnicity demographic data for the Phase 2 trial (post-intervention) will be compared with the Phase 3 trial (pre-intervention) using the chi-square statistical test. Assuming significant results, a Z-test will then be used to assess the proportions of each race and ethnicity group.

A Cost, Time, and Demographic Analysis of Participant Recruitment and Urine Sample Collection Through Social Media Optimization.

Clinical research can be expensive and time consuming due to high associated costs and/or duration of the study. We hypothesized that urine sample collection using online recruitment and engagement of research participants via social medial has the potential to reach a large population in a small timeframe, at a reasonable cost. We performed a retrospective cost analysis of a cohort study comparing cost per sample and time per sample for both online and clinically recruited participants for urine sample collection. During this time, cost data were collected based on study associated costs from invoices and budget spreadsheets. The data were subsequently analyzed using descriptive statistics. Each sample collection kit contained 3 urine cups, 1 for the disease sample and 2 for control samples. Out of the 3,576 (1,192 disease + 2,384 control) total sample cups mailed, 1,254 (695 control) samples were returned. Comparatively, the 2 clinical sites collected 305 samples. Although the initial startup cost of online recruitment was higher, cost per sample for online recruited was found to be $81.45 compared to $398.14 for clinic sample. We conducted a nationwide, contactless, urine sample collection through online recruitment in the midst of the COVID-19 pandemic. Results were compared with the samples collected in the clinical setting. Online recruitment can be utilized to collect urine samples rapidly, efficiently, and at a cost per sample that was 20% of an in-person clinic, and without risk of COVID-19 exposure.

Socio-economic and behavioral «portrait» of patients with myocardial infarction

Aim. To identify the specifics of socioeconomic status and behavioral patterns in patients with myocardial infarction (MI) compared with the data of regional epidemiological study participants.Material and methods. The study included participants aged 35–70 years permanently residing in the Kemerovo city or Kemerovo region. The study group consisted of patients with MI (n = 60), and the comparison group consisted of clinical and epidemiological study participants (the study was conducted by the Research Institute for Complex Issues of Cardiovascular Diseases in 2015–2020 (n = 752). After matching, the study group included 28 patients; the comparison group included 428 participants. The data were collected using a questionnaire to identify the characteristics that determine the socioeconomic and behavioral «portrait» of the participants, their health status. Food Frequency Questionnaire was used to assess how often each food item was consumed over a specified period of time. International Questionnaire on Physical Activity was used to measure health-related physical activity of the subjects.Results. All participants (with MI and from the epidemiological study) display negative behavior patterns that greatly increase the risk of experiencing cardiovascular events. However, patients with MI had a higher incidence of type 2 diabetes mellitus in the medical history (p = 0.044), prior MI, peripheral arterial disease (p = 0.001); obesity was noted less frequently (p = 0.014). Patients with MI were more likely to be prescribed antihypertensive drugs (p = 0.001), at the time of the survey they were more likely to be active (p = 0.017) and passive (p = 0.001) smokers. Alcohol consumption at the time of the survey was noted more frequently in patients with MI (p = 0.040), while the majority of respondents from the general population did not consume alcohol (p = 0.038). Patients with MI were less likely to display low physical activity at work 7 days prior to hospitalization (p = 0.001). Simultaneously, patients with MI were less likely to consume cooked and seasonal vegetables, seasonal fruits (p = 0.001). Moreover, patients with MI were more likely to incorporate fatty (p = 0.003) and low-fat dairy products (p = 0.001), lean (p = 0.013) and fatty meat (p = 0.036) in their diet.Conclusion. The established patterns of behavior in patients with MI and in the general population of the Kemerovo region do not differ significantly. A large number of people residing in Russia routinely makes unhealthy lifestyle choices, however, several «pro-atherogenic» characteristics can be identified in patients with MI.

POS-038 ALTERNATIVE COMPLEMENT PATHWAY INHIBITION WITH IPTACOPAN TO ARREST DISEASE PROGRESSION IN C3 GLOMERULOPATHY (APPEAR-C3G): A PHASE 3 STUDY

IntroductionComplement 3 glomerulopathy (C3G) is a rare kidney disease characterized by dysregulation of the alternative pathway (AP) of the complement system. Around 50% of patients progress to kidney failure within 10 years of diagnosis. Currently, there are no approved therapies for C3G. Iptacopan (LNP023) is an oral, first-in-class, potent and selective inhibitor of factor B, a key regulator of the AP. In a previously reported phase 2 study, 12 weeks treatment with iptacopan was associated with 45% reduction in proteinuria (p=0.0003), stabilization of eGFR in native kidneys of C3G patients and reduction in C3 deposit scores on renal biopsy in patients with recurrent C3G after transplantation (p=0.03). Iptacopan showed a favorable safety and tolerability profile in both cohorts.MethodsResultsRecruitment ongoing.ConclusionsThis Phase 3 study will provide valuable evidence towards the efficacy and safety of iptacopan in C3G patients with native kidney disease.Conflict of interest Corporate sponsored research or other substantive relationships:Richard JH Smith: research funding from NIH, consultant for Novartis. David G Kavanagh: grant support from Medical Research Council Wellcome Trust Kidney Research UK Complement UK Fight For Sight, Macular Society, consultant for Silence Therapeutics, Alexion Pharmaceuticals, Novartis, Apellis and Sarepta, Founder and Scientific Advisor, Gyroscope Therapeutics, Advisory board involvement includes Novartis, Sarepta Gyroscope Therapeutics, Silence Therapeutics. Ronda Tawfik, Angelo J Trapani, Yaqin Wang, Nicholas Webb and Matthias Meier are employees and stockholders of Novartis. Marina Vivarelli: honoraria for advisory boards and consulting fees, participation in clinical studies sponsored by the following pharmaceutical companies: Achillion Alexion Apellis Bayer Catalyst Novartis Roche Retrophin/Travere. Andrew S Bomback: consulting honoraria from Achillion, Alexion, Chemocentryx, Novartis, Silence, Catalyst, and Principio. IntroductionComplement 3 glomerulopathy (C3G) is a rare kidney disease characterized by dysregulation of the alternative pathway (AP) of the complement system. Around 50% of patients progress to kidney failure within 10 years of diagnosis. Currently, there are no approved therapies for C3G. Iptacopan (LNP023) is an oral, first-in-class, potent and selective inhibitor of factor B, a key regulator of the AP. In a previously reported phase 2 study, 12 weeks treatment with iptacopan was associated with 45% reduction in proteinuria (p=0.0003), stabilization of eGFR in native kidneys of C3G patients and reduction in C3 deposit scores on renal biopsy in patients with recurrent C3G after transplantation (p=0.03). Iptacopan showed a favorable safety and tolerability profile in both cohorts. Complement 3 glomerulopathy (C3G) is a rare kidney disease characterized by dysregulation of the alternative pathway (AP) of the complement system. Around 50% of patients progress to kidney failure within 10 years of diagnosis. Currently, there are no approved therapies for C3G. Iptacopan (LNP023) is an oral, first-in-class, potent and selective inhibitor of factor B, a key regulator of the AP. In a previously reported phase 2 study, 12 weeks treatment with iptacopan was associated with 45% reduction in proteinuria (p=0.0003), stabilization of eGFR in native kidneys of C3G patients and reduction in C3 deposit scores on renal biopsy in patients with recurrent C3G after transplantation (p=0.03). Iptacopan showed a favorable safety and tolerability profile in both cohorts. Methods ResultsRecruitment ongoing. Recruitment ongoing. ConclusionsThis Phase 3 study will provide valuable evidence towards the efficacy and safety of iptacopan in C3G patients with native kidney disease.Conflict of interest Corporate sponsored research or other substantive relationships:Richard JH Smith: research funding from NIH, consultant for Novartis. David G Kavanagh: grant support from Medical Research Council Wellcome Trust Kidney Research UK Complement UK Fight For Sight, Macular Society, consultant for Silence Therapeutics, Alexion Pharmaceuticals, Novartis, Apellis and Sarepta, Founder and Scientific Advisor, Gyroscope Therapeutics, Advisory board involvement includes Novartis, Sarepta Gyroscope Therapeutics, Silence Therapeutics. Ronda Tawfik, Angelo J Trapani, Yaqin Wang, Nicholas Webb and Matthias Meier are employees and stockholders of Novartis. Marina Vivarelli: honoraria for advisory boards and consulting fees, participation in clinical studies sponsored by the following pharmaceutical companies: Achillion Alexion Apellis Bayer Catalyst Novartis Roche Retrophin/Travere. Andrew S Bomback: consulting honoraria from Achillion, Alexion, Chemocentryx, Novartis, Silence, Catalyst, and Principio. This Phase 3 study will provide valuable evidence towards the efficacy and safety of iptacopan in C3G patients with native kidney disease.

Leveraging patient engagement to optimize a phase 3 clinical trial design, study participation and recruitment for women diagnosed with triple-negative breast cancer (TNBC).

1073 Background: The importance of Patient Engagement (PE) on clinical trial design is well established. PE in oncology medicines development can serve many purposes including obtaining input on trial design/procedures, identifying recruitment challenges and barriers to participation, and understanding retention strategies. Designing a clinical trial with procedures that have been confirmed as acceptable to participants is also likely to improve patient adherence to treatments. Triple-Negative Breast Cancer (TNBC) is a virulent subtype associated with early onset and increased risk of early recurrence and accounts for 15% to 20% of breast cancers. In addition, a higher risk exists in premenopausal and Black women. Chemotherapy is the mainstay of curative therapy recommended by guidelines. The aim was to obtain insights from patients to inform key aspects of a clinical study design including choice of chemotherapy regimen, study feasibility and recruitment strategies. Methods: Two groups of US women (N = 20) ages 28-54; (race 55% Caucasian, 30% African American, 10% Hispanic, 5% Native American) diagnosed with Stage IIb-IV TNBC and in active or completed treatment were recruited to participate in two in person IRB approved sessions. Trained 3rd party facilitators used qualitative methods to elicit patient feedback. Preliminary research included interviews with key stakeholders, including TNBC advocacy group leaders and a review of online patient communities. Patients reviewed a study design with an investigational agent every 3 weeks plus chemotherapy (nab-paclitaxel; paclitaxel) or placebo plus chemotherapy. Results: Patient reaction to the choice of taxane chemotherapy in the standard of care arm was neutral to negative. Approximately 50% of the patients identified taxane treatment as a barrier to participation. All patients requested flexibility in treatment choices, clear information about required tests and visits, and more diversity in recruitment materials. Black and Hispanic women impacted by TNBC did not feel they had equal access to clinical trials due to race, rural location, and other factors. Patient insights reinforced the decision to add another standard-of-care option (carboplatin plus gemcitabine) as a treatment arm to the trial design and was confirmed with investigators. Patient feedback was incorporated into the trial along with additional strategies to support recruitment of diverse patients in the clinical study. Conclusions: On November 13, 2020 the FDA approved this regimen in the label for pembrolizumab in combination with chemotherapy, as the 1st line treatment in women with locally recurrent or metastatic TNBC. Both patients and physicians perceived that a flexible chemotherapy backbone was a benefit.

Ethical Issues in Social Media Recruitment for Clinical Studies: Ethical Analysis and Framework.

BackgroundSocial media recruitment for clinical studies holds the promise of being a cost-effective way of attracting traditionally marginalized populations and promoting patient engagement with researchers and a particular study. However, using social media for recruiting clinical study participants also poses a range of ethical issues.ObjectiveThis study aims to provide a comprehensive overview of the ethical benefits and risks to be considered for social media recruitment in clinical studies and develop practical recommendations on how to implement these considerations.MethodsOn the basis of established principles of clinical ethics and research ethics, we reviewed the conceptual and empirical literature for ethical benefits and challenges related to social media recruitment. From these, we derived a conceptual framework to evaluate the eligibility of social media use for recruitment for a specific clinical study.ResultsWe identified three eligibility criteria for social media recruitment for clinical studies: information and consent, risks for target groups, and recruitment effectiveness. These criteria can be used to evaluate the implementation of a social media recruitment strategy at its planning stage. We have discussed the practical implications of these criteria for researchers.ConclusionsThe ethical challenges related to social media recruitment are context sensitive. Therefore, social media recruitment should be planned rigorously, taking into account the target group, the appropriateness of social media as a recruitment channel, and the resources available to execute the strategy.

Examining the association of life course neurocognitive ability with real-world functioning in schizophrenia-spectrum disorders

There is considerable variability in neurocognitive functioning within schizophrenia-spectrum disorders, and neurocognitive performance ranges from severe global impairment to normative performance. Few investigations of neurocognitive clusters have considered the degree to which deterioration relative to premorbid neurocognitive abilities is related to key illness characteristics. Moreover, while neurocognition and community functioning are strongly related, understanding of the sources of variability in the association between these two domains is also limited; it is unknown what proportion of participants would over-perform or under-perform the level of functioning expected based on current neurocognitive performance vs. lifelong attainment. This study examined data from 954 outpatients with schizophrenia-spectrum disorders across three previous studies. Neurocognition, community functioning, and symptoms were assessed. Neurocognitive subgroups were created based on current neurocognition, estimated premorbid IQ, and degree of deterioration from premorbid using z-score cut-offs; functional subgroups were created with cluster analysis based on the Specific Level of Functioning Scale and current neurocognition. The sample was neurocognitively heterogeneous; 65% displayed current neurocognitive impairment and 84% experienced some level of deterioration. Thirty percent of our sample was relatively higher functioning despite significant neurocognitive impairment. Individuals with better community functioning, regardless of neurocognitive performance, had lower symptom severity compared to those with worse functioning. These results highlight the variability in neurocognition and its role in functioning. Understanding individual differences in neurocognitive and functional profiles and the interaction between prior and current cognitive functioning can guide individualized treatment and selection of participants for clinical treatment studies.

Self-reporting of psychiatric illness in an online patient registry is a good indicator of the existence of psychiatric illness

Online registries offer many advantages for research, including the ability to efficiently assess large numbers of individuals and identify potential participants for clinical trials and genetic studies. Of particular interest is the validity and utility of self-endorsement of psychiatric disorders in online registries, which, while increasingly more common, remain understudied. We thus assessed the comparability of prevalence estimated from self-endorsement of psychiatric disorders in one such registry, the Brain Health Registry (BHR) to prevalence computed from large US-based epidemiological studies and the degree to which BHR participants report psychiatric disorders consistently. We also examined the concordance between self-report and clinically determined diagnoses of various DSM-5 psychiatric disorders in a subset of participants who underwent direct assessments and identified possible reasons for discordance.Rates of self-reported psychiatric disorders were closest to previously reported population prevalence rates when endorsed at multiple timepoints, and accuracy was at least 70% for all except Hoarding Disorder as compared to the clinical diagnoses. Clinical data suggested that self-endorsement of a given psychiatric diagnosis was indicative of the presence of a closely related condition, although not necessarily for the specific disorder, with the exception of major depressive disorder, panic disorder, and hoarding disorder, which had high positive predictive values (85%, 73%, 100%, respectively).We conclude that self-reporting of psychiatric conditions in an online setting is a fair indicator of psychopathology, but should be accompanied by more in-depth interviews if using data from a participant for a specific disorder.

Attitudes and Expectations of Clinical Research Participants Toward Digital Health and Mobile Dietary Assessment Tools: Cross-Sectional Survey Study.

BackgroundThe adoption of health technologies is key to empower research participants and collect quality data. However, the acceptance of health technologies is usually evaluated in patients or healthcare practitioners, but not in clinical research participants.MethodsA 27-item online questionnaire was provided to the 11,695 members of a nutrition clinical research participant database from the Nantes area (France), to assess (1) participants' social and demography parameters, (2) equipment and usage of health apps and devices, (3) expectations in research setting and (4) opinion about the future of clinical research. Each item was described using frequency and percentage overall and by age classes. A global proportion comparison was performed using chi-square or Fisher-exact tests.ResultsA total of 1529 respondents (81.0% women, 19.0% men) completed the survey. Main uses of health apps included physical activity tracking (54.7%, age-related group difference, p < 0.001) and food quality assessment (45.7%, unrelated to age groups). Overall, 20.4% of respondents declared owning a connected wristband or watch. Most participants (93.8%) expected the use of connected devices in research. However, protection of personal data (37.5%), reliability (35.5%) and skilled use of devices (28.5%) were perceived as the main barriers. Most participants (93.3%) would agree to track their food intake using a mobile app, and 80.5% would complete it for at least a week while taking part in a clinical study. Only 13.2% would devote more than 10 min per meal to such record. A majority (60.4%) of respondents would accept to share their social media posts in an anonymous way and most (82.2%) of them would accept to interact with a chatbot for research purposes.ConclusionsOur cross-sectional study suggests that clinical study participants are enthusiastic about all forms of digital health technologies and participant-centered studies but remain concerned about the use of personal data. Repeated assessments are suggested to evaluate the research participant's interest in technologies following the increase in use and demand for innovative health services during the pandemic of COVID-19.

What Do Physicians Think About the Use of Telemedicine to Recruit and Assess Participants in mHealth-Related Clinical Studies as a Consequence of the COVID-19 Pandemic?

Objectives: To evaluate physician's opinion and availability to participate in mHealth-related clinical studies with patient recruitment and assessment via telemedicine and to identify characteristics associated with the willingness to participate. Methods: Cross-sectional, observational study, based on an anonymous web survey conducted in May-Jun of 2020 to 237 physicians, from Portugal and Spain that collaborated with an asthma mHealth project (INSPIRERS). Results: Response rate was 51% (n = 120). Most (74%, n = 89) physicians were available to participate in such studies, but 62% anticipated lower recruiting capacity and 40% increased difficulty in obtaining quality data. Physicians aged ≤40 years, from secondary care (vs. general practitioners) and that used apps in personal life or clinical practice were more likely to be available. Conclusions: Three-quarters of the physicians were available to participate in mHealth-related clinical studies with patient recruitment and assessment through telemedicine. Age group, medical specialty, and app use were associated with the willingness to participate.

Special Report: Ethical Decision-Making in Contemporary Psychiatric Practice—An Evolving Challenge

Special Report: Ethical Decision-Making in Contemporary Psychiatric Practice—An Evolving Challenge