Advancing workforce diversity by leveraging the Clinical and Translational Science Awards (CTSA) program.

Clinical trials continue to disproportionately underrepresent people of color. Increasing representation of diverse backgrounds among clinical research personnel has the potential to yield greater representation in clinical trials and more efficacious medical interventions by addressing medical mistrust. In 2019, North Carolina Central University (NCCU), a Historically Black College and University with a more than 80% underrepresented student population, established the Clinical Research Sciences Program with support from the Clinical and Translational Science Awards (CTSA) program at neighboring Duke University. This program was designed to increase exposure of students from diverse educational, racial, and ethnic backgrounds to the field of clinical research, with a special focus on health equity education. In the first year, the program graduated 11 students from the two-semester certificate program, eight of whom now hold positions as clinical research professionals. This article describes how leveraging the CTSA program helped NCCU build a framework for producing a highly trained, competent, and diverse workforce in clinical research responsive to the call for increased diversity in clinical trial participation.

Assessment of Outcomes After Stopping Tyrosine Kinase Inhibitors Among Patients With Chronic Myeloid Leukemia: A Nonrandomized Clinical Trial.

IMPORTANCE: Tyrosine kinase inhibitors (TKIs) have been associated with improved survival of patients with chronic myeloid leukemia (CML) but are also associated with adverse effects, especially fatigue and diarrhea. Discontinuation of TKIs is safe and is associated with the successful achievement of treatment-free remission (TFR) for some patients. OBJECTIVE: To evaluate molecular recurrence (MRec) and patient-reported outcomes (PROs) after TKI discontinuation for US patients with CML. DESIGN, SETTING, AND PARTICIPANTS: The Life After Stopping TKIs (LAST) study was a prospective single-group nonrandomized clinical trial that enrolled 172 patients from 14 US academic medical centers from December 18, 2014, to December 12, 2016, with a minimum follow-up of 3 years. Participants were adults with chronic-phase CML whose disease was well controlled with imatinib, dasatinib, nilotinib, or bosutinib. Statistical analysis was performed from August 13, 2019, to March 23, 2020. INTERVENTION: Discontinuation of TKIs. MAIN OUTCOMES AND MEASURES: Molecular recurrence, defined as loss of major molecular response (BCR-ABL1 International Scale ratio >0.1%) by central laboratory testing, and PROs (Patient-Reported Outcomes Measurement Information System computerized adaptive tests) were monitored. Droplet digital polymerase chain reaction (ddPCR) was performed on samples with undetectable BCR-ABL1 by standard real-time quantitative polymerase chain reaction (RQ-PCR). RESULTS: Of 172 patients, 89 were women (51.7%), and the median age was 60 years (range, 21-86 years). Of 171 patients evaluable for molecular analysis, 112 (65.5%) stayed in major molecular response, and 104 (60.8%) achieved TFR. Undetectable BCR-ABL1 by either ddPCR or RQ-PCR at the time of TKI discontinuation (hazard ratio, 3.60; 95% CI, 1.99-6.50; P < .001) and at 3 months (hazard ratio, 5.86; 95% CI, 3.07-11.1; P < .001) was independently associated with MRec. Molecular recurrence for patients with detectable BCR-ABL1 by RQ-PCR was 50.0% (14 of 28), undetectable BCR-ABL1 by RQ-PCR but detectable by ddPCR was 64.3% (36 of 56), and undetectable BCR-ABL1 by both ddPCR and RQ-PCR was 10.3% (9 of 87) (P ≤ .001). Of the 112 patients in TFR at 12 months, 90 (80.4%) had a clinically meaningful improvement in fatigue, 39 (34.8%) had a clinically meaningful improvement in depression, 98 (87.5%) had a clinically meaningful improvement in diarrhea, 24 (21.4%) had a clinically meaningful improvement in sleep disturbance, and 5 (4.5%) had a clinically meaningful improvement in pain interference. Restarting a TKI resulted in worsening of PROs. CONCLUSIONS AND RELEVANCE: In this study, TKI discontinuation was safe, and 60.8% of patients remained in TFR. Discontinuation of TKIs was associated with improvements in PROs. These findings should assist patients and physicians in their decision-making regarding discontinuation of TKIs. Detectable BCR-ABL1 by RQ-PCR or ddPCR at the time of TKI discontinuation was associated with higher risk of MRec; clinical application of this finding should be confirmed in other studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02269267.

A New Brief Clinical Assessment of Lower Urinary Tract Symptoms for Women and Men: LURN SI-10.

PURPOSE: Lower urinary tract symptoms are common in men and women. Members of the LURN (Lower Urinary Tract Dysfunction Research Network) sought to create a brief, clinically relevant tool to improve existing measurements of lower urinary tract symptoms in men and women. MATERIALS AND METHODS: Using a modified Delphi methodology during an expert consensus meeting we reduced the LURN CASUS (Comprehensive Assessment of Self-Reported Urinary Symptoms) questionnaire to a brief set of clinically relevant items measuring lower urinary tract symptoms. The sum score of these items was evaluated by comparing it to the AUA SI (American Urological Association Symptom Index), the UDI-6 (Urinary Distress Inventory Short Form) in women only and the CASUS lower urinary tract symptoms screening questions using the Pearson correlation, regression analysis and ROC curves. RESULTS: The LURN SI-10 (10-Item LURN Symptom Index) assesses urinary frequency, nocturia, urgency, incontinence, bladder pain, voiding and post-micturition symptoms (score range 0 to 38). The correlation between LURN SI-10 and AUA SI scores was 0.77 in men and 0.70 in women. The UDI-6 and the LURN SI-10 correlated highly in women (r=0.76). The LURN SI-10 showed good accuracy to predict moderate and severe lower urinary tract symptoms as defined by the AUA SI (ROC AUC range 0.82-0.90). Similar accuracy was shown in predicting different levels of symptom status using the UDI-6 (AUC range 0.84-0.86). CONCLUSIONS: The LURN SI-10 correlates well with the AUA SI and the UDI-6. It includes items related to a broader spectrum of lower urinary tract symptoms, particularly incontinence, bladder pain and post-micturition symptoms, and it applies to men and women.

Public views regarding the responsibility of patients, clinicians, and institutions to participate in research in the United States.

BACKGROUND: The need for more and better evidence to inform clinical decision making among all stakeholders has fueled calls for creating learning healthcare systems. The successful realization of a learning healthcare system seems to assume that various parties have a responsibility to participate in learning activities, including research. The objective of this study was to determine whether members of the general public perceive an ethical responsibility to participate in pragmatic clinical research that would be inherent to a learning health system. METHODS: A total of 2994 English-speaking adults completed a nationally representative online survey. RESULTS: About two-thirds of respondents were relatively neutral regarding a responsibility for themselves and others to participate in research; the remainder felt that they and others did not have a responsibility to participate in research. CONCLUSIONS: Efforts to justify and develop a robust learning health system in an ethically acceptable fashion need to take these findings into account.

The Comprehensive Assessment of Self-Reported Urinary Symptoms: A New Tool for Research on Subtypes of Patients with Lower Urinary Tract Symptoms.

PURPOSE: To improve the potential for finding clinically important subtypes of patients with lower urinary tract symptoms we developed the CASUS (Comprehensive Assessment of Self-reported Urinary Symptoms). We used it to present data on the experiences of lower urinary tract symptoms in treatment seeking women and men from a prospective observational cohort. MATERIALS AND METHODS: We created an initial list of lower urinary tract symptoms that were confirmed in 22 qualitative interviews with providers, and 88 qualitative interviews with care seeking and noncare seeking women and men with lower urinary tract symptoms. Items from extant measures were adopted and revised, and new items were developed. All items were evaluated for understanding in 64 cognitive interviews. Items were administered to a prospective cohort of female and male patients with lower urinary tract symptoms who were seeking care. Analyses were done to describe item response distributions and correlations among item responses separately for women and men. RESULTS: A total of 444 males and 372 females provided responses to the CASUS. Several sets of items showed different relationships for women compared to men. In particular the associations between sensation related items and incontinence related items were generally positive among females but often negative among males. CONCLUSIONS: After using an intensive development process the CASUS addresses a wide range of lower urinary tract symptoms. It should help identify clinically important subtypes of patients. Further, item collection can provide the foundation for shorter measures for use in the clinic and as trial end points.

Inflammatory Bowel Diseases Can Adversely Impact Domains of Sexual Function Such as Satisfaction with Sex Life.

BACKGROUND: Aspects of sexual health, which can be adversely affected by chronic disease, have been inadequately explored in inflammatory bowel disease (IBD). AIMS: We evaluated patient-reported interest in sexual activity and satisfaction with sex life in a large cohort of IBD patients. METHODS: We conducted a cross-sectional study within the Crohn's and Colitis Foundation Partners Internet cohort. Sequential participants completed a 6-question supplemental online survey to examine sexual interest and satisfaction using the Patient-Reported Outcome Measurement Information System® (PROMIS®) Sexual Function and Satisfaction measures. One-sample t tests were used to compare interest and satisfaction scores to general population norms. RESULTS: Among 2569 individuals, 1639 had Crohn's disease (CD), 930 had ulcerative colitis (UC) or indeterminate colitis, and 71% were women. Mean PROMIS scores for sexual interest were comparable to the general US population in men (CD: 49 and UC: 50 vs. population mean 50) and women (CD: 41 and UC: 40 vs. population mean 42). However, sexual satisfaction scores were lower than the US population in men (CD: 48 and UC: 48 vs. 51) and women (CD: 47 and UC: 46 vs. 49), p < 0.01 for both. Older age, disease activity, depression, anxiety, and pain were associated with lower interest and satisfaction and lowered IBD-specific quality of life. CONCLUSIONS: IBD patients in a large online survey had similar levels of sexual interest but decreased sexual satisfaction compared to the general population. Exploring these sexual health domains during clinical encounters can aid in improving IBD quality of life.

Prevalence and Characteristics of Urinary Incontinence in a Treatment Seeking Male Prospective Cohort: Results from the LURN Study.

PURPOSE: Male urinary incontinence is thought to be infrequent. We sought to describe the prevalence of urinary incontinence in a male treatment seeking cohort enrolled in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network). MATERIALS AND METHODS: Study inclusion and exclusion criteria, including men with prostate cancer or neurogenic bladder, were previously reported. LURN participants prospectively completed questionnaires regarding lower urinary tract symptoms and other clinical variables. Men were grouped based on incontinence type, including 1) no urinary incontinence, 2) post-void dribbling only and 3) urinary incontinence. Comparisons were made using ANOVA and multivariable regression. RESULTS: Of the 477 men 24% reported no urinary incontinence, 44% reported post-void dribbling only and 32% reported urinary incontinence. African American men and those with sleep apnea were more likely to be in the urinary incontinence group than in the no urinary incontinence group (OR 3.2, p = 0.02 and OR 2.73, p = 0.003, respectively). Urinary incontinence was associated with significantly higher bother compared to men without leakage (p <0.001). Compared to men without urinary incontinence and men with only post-void dribbling those with urinary incontinence were significantly more likely to report higher scores (more severe symptoms) on the PROMIS (Patient-Reported Outcomes Measurement Information System) questionnaires regarding bowel issues, depression and anxiety than men without urinary incontinence (p <0.01). CONCLUSIONS: Urinary incontinence is common among treatment seeking men. This is concerning because the guideline recommended questionnaires to assess male lower urinary tract symptoms do not query for urinary incontinence. Thus, clinicians may be missing an opportunity to intervene and improve patient care. This provides a substantial rationale for a new or updated symptom questionnaire which provides a more comprehensive symptom assessment.

Pragmatic clinical trials embedded in healthcare systems: generalizable lessons from the NIH Collaboratory.

BACKGROUND: The clinical research enterprise is not producing the evidence decision makers arguably need in a timely and cost effective manner; research currently involves the use of labor-intensive parallel systems that are separate from clinical care. The emergence of pragmatic clinical trials (PCTs) poses a possible solution: these large-scale trials are embedded within routine clinical care and often involve cluster randomization of hospitals, clinics, primary care providers, etc. Interventions can be implemented by health system personnel through usual communication channels and quality improvement infrastructure, and data collected as part of routine clinical care. However, experience with these trials is nascent and best practices regarding design operational, analytic, and reporting methodologies are undeveloped. METHODS: To strengthen the national capacity to implement cost-effective, large-scale PCTs, the Common Fund of the National Institutes of Health created the Health Care Systems Research Collaboratory (Collaboratory) to support the design, execution, and dissemination of a series of demonstration projects using a pragmatic research design. RESULTS: In this article, we will describe the Collaboratory, highlight some of the challenges encountered and solutions developed thus far, and discuss remaining barriers and opportunities for large-scale evidence generation using PCTs. CONCLUSION: A planning phase is critical, and even with careful planning, new challenges arise during execution; comparisons between arms can be complicated by unanticipated changes. Early and ongoing engagement with both health care system leaders and front-line clinicians is critical for success. There is also marked uncertainty when applying existing ethical and regulatory frameworks to PCTS, and using existing electronic health records for data capture adds complexity.

Sexual function and satisfaction among heterosexual and sexual minority U.S. adults: A cross-sectional survey.

BACKGROUND: Despite known health disparities for sexual minorities, few studies have described sexual function by sexual orientation using a robust approach to measurement of sexual function. We compared recent sexual function and satisfaction by sexual orientation among English-speaking US adults. METHODS AND FINDINGS: Cross-sectional surveys were administered by KnowledgePanel® (GfK), an online panel that uses address-based probability sampling and is representative of the civilian, noninstitutionalized US population. Data were collected in 2013 from the general population (n = 3314, 35% response rate) and in 2014 from self-identified lesbian, gay, and bisexual adults (n = 1011, 50% response rate). Sexual function and satisfaction were measured using the Patient-Reported Outcomes Measurement Information System® Sexual Function and Satisfaction measure version 2.0 (PROMIS SexFS v2). The PROMIS SexFS v2 is a comprehensive, customizable measurement system with evidence for validity in diverse populations. A score of 50 (SD 10) on each domain corresponds to the average for US adults sexually active in the past 30 days. We adjusted all statistics for the complex sample designs and report differences within each sex where the 95% CIs do not overlap, corresponding to p<0.01. Among US men who reported any sexual activity in the past 30 days, there were no differences in erectile function or orgasm-ability. Compared to heterosexual men, sexual minority men reported higher oral dryness and lower orgasm-pleasure and satisfaction. Compared to heterosexual men, gay men reported lower interest, higher anal discomfort and higher oral discomfort. Among sexually active women, there were no differences in the domains of vulvar discomfort-clitoral, orgasm-pleasure, or satisfaction. Compared to heterosexual women, sexual minority women reported higher oral dryness. Lesbian women reported lower vaginal discomfort than other women; lesbian women reported higher lubrication and orgasm-ability than heterosexual women. Bisexual women reported higher interest, higher vulvar discomfort-labial and higher anal discomfort than other women, as well as higher oral discomfort compared to heterosexual women. CONCLUSIONS: Recent sexual function and satisfaction differed by sexual orientation among US adults. Sexual minority men and women had decrements in domains of sexual function that have not traditionally been included in multi-dimensional self-report measures. Clinicians should make themselves aware of their patients' sexual concerns and recognize that sexual minority patients may be more vulnerable to certain sexual difficulties than heterosexual patients.

Assessment of vulvar discomfort with sexual activity among women in the United States.

BACKGROUND: Multidimensional self-report measures of sexual function for women do not include the assessment of vulvar discomfort, limiting our understanding of its prevalence. In an effort to improve the measurement of patient-reported health, the National Institutes of Health funded the creation of the Patient Reported Outcomes Measurement Information System (PROMIS). This included the development of the PROMIS Sexual Function and Satisfaction measure, and version 2.0 of the Sexual Function and Satisfaction measure included 2 scales to measure vulvar discomfort with sexual activity. OBJECTIVES: The objectives of the study were to describe the development of 2 self-reported measures of vulvar discomfort with sexual activity, describe the relationships between these scales and scales for lubrication and vaginal discomfort, and report the prevalence of vulvar discomfort with sexual activity in a large, nationally representative sample of US women. STUDY DESIGN: We followed PROMIS measure development standards, including qualitative development work with patients and clinicians and psychometric evaluation of candidate items based on item response theory, in a probability sample of 1686 English-speaking US adult women. We tested 16 candidate items on vulvar discomfort. We present descriptive statistics for these items, correlation coefficients among the vulvar and vaginal scales, and mean PROMIS scores with 95% confidence intervals separately by menopausal status for the 1046 women who reported sexual activity in the past 30 days. RESULTS: Based on the psychometric evaluation of the candidate items, we created 2 separate 4 item scales, one to measure labial discomfort and pain and one to measure clitoral discomfort and pain. Additional items not included in the scales assess pain quality, numbness, and bleeding. The correlations between the lubrication, vaginal discomfort, and the 2 vulvar discomfort measures ranged from 0.46 to 0.77, suggesting that these measures represent related yet distinct concepts. In our nationally representative sample, 1 in 5 US women endorsed some degree of vulvar discomfort with sexual activity in the past 30 days. Menopausal status was associated with lower lubrication and higher vaginal discomfort but not with vulvar discomfort. CONCLUSION: The PROMIS Vulvar Discomfort with Sexual Activity-Labial and Vulvar Discomfort with Sexual Activity-Clitoral scales are publicly available for use in research and clinical settings. There is limited overlap between vulvar discomfort and lubrication or vaginal discomfort. The importance of measuring vulvar discomfort as part of a comprehensive assessment of sexual function is underscored by its prevalence.

Sexual Satisfaction and the Importance of Sexual Health to Quality of Life Throughout the Life Course of U.S. Adults.

INTRODUCTION: Discussions about sexual health are uncommon in clinical encounters, despite the sexual dysfunction associated with many common health conditions. Understanding of the importance of sexual health and sexual satisfaction in U.S. adults is limited. AIM: To provide epidemiologic data on the importance of sexual health for quality of life and people's satisfaction with their sex lives and to examine how each is associated with demographic and health factors. METHODS: Data are from a cross-sectional self-report questionnaire from a sample of 3,515 English-speaking U.S. adults recruited from an online panel that uses address-based probability sampling. MAIN OUTCOME MEASURES: We report ratings of importance of sexual health to quality of life (single item with five-point response) and the Patient-Reported Outcomes Measurement Information System Satisfaction With Sex Life score (five items, each with five-point responses, scores centered on the U.S. mean). RESULTS: High importance of sexual health to quality of life was reported by 62.2% of men (95% CI = 59.4-65.0) and 42.8% of women (95% CI = 39.6-46.1, P < .001). Importance of sexual health varied by sex, age, sexual activity status, and general self-rated health. For the 55% of men and 45% of women who reported sexual activity in the previous 30 days, satisfaction with sex life differed by sex, age, race-ethnicity (among men only), and health. Men and women in excellent health had significantly higher satisfaction than participants in fair or poor health. Women with hypertension reported significantly lower satisfaction (especially younger women), as did men with depression or anxiety (especially younger men). CONCLUSION: In this large study of U.S. adults' ratings of the importance of sexual health and satisfaction with sex life, sexual health was a highly important aspect of quality of life for many participants, including participants in poor health. Moreover, participants in poorer health reported lower sexual satisfaction. Accordingly, sexual health should be a routine part of clinicians' assessments of their patients. Health care systems that state a commitment to improving patients' overall health must have resources in place to address sexual concerns. These resources should be available for all patients across the lifespan.

Community consultation for prehospital research: experiences of study coordinators and principal investigators.

OBJECTIVE: To assess principal investigators' and study coordinators' views and experiences regarding community consultation in a multicenter trial of prehospital treatment for status epilepticus conducted under an exception from informed consent for research in emergency settings. METHODS: Principal investigators and study coordinators at all 17 hubs for the Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) were invited to complete a web-based survey regarding community consultation at their site for RAMPART. Major domains included 1) perceived goals of community consultation, 2) experiences with and views of community consultation methods used, 3) interactions with IRB regarding community consultation, and 4) general satisfaction and lessons learned. Descriptive statistics were tabulated for Likert scale data; relevant themes were reported for text-based data. RESULTS: Twenty-eight individuals (16 coordinators and 12 investigators) representing all 17 RAMPART hubs completed the survey. Respondents considered multiple community consultation goals to be important, with least support for the role of community consultation in altering study design. All sites used multiple methods (median = 5). The most widely used, and generally favored, method was attending previously scheduled meetings of existing groups. Respondents expressed frustration with low attendance and responsiveness at open public meetings. CONCLUSIONS: Coordinators and investigators in this trial viewed community consultation efforts as successful but reported real challenges generating public interest. Individuals with the condition under study were found to be more engaged and supportive of the trial. Respondents endorsed numerous potential goals of the community consultation process and often combined methods to achieve these goals.

Patient time costs associated with sensor-augmented insulin pump therapy for type 1 diabetes: results from the STAR 3 randomized trial.

BACKGROUND: Sensor-augmented pump therapy (SAPT) leads to lower glycated hemoglobin levels than multiple daily injections of insulin (MDI) in patients with type 1 diabetes. Patient time and costs associated with SAPT are not known. OBJECTIVE: We compared time spent on diabetes-related care, changes in time, and associated patient time costs between patients randomly assigned to SAPT or MDI. DESIGN, SETTING, AND PARTICIPANTS. During a 52-week clinical trial, participants aged 7 to 70 years (n = 483) reported total time per week spent on diabetes-related care. MEASUREMENTS: Patient time, including comparisons during pump initiation, 52-week patient time costs, and changes in weekly time estimates after pump initiation. RESULTS: At baseline, patients in the MDI group reported spending an average of 4.0 hours per week on diabetes-related care. During the pump initiation period (weeks 1-7), SAPT patients spent 1.9 hours more per week than MDI patients (95% confidence interval [CI], 1.2-2.6). After the initiation period (weeks 8-52), SAPT patients spent 1 hour more per week (95% CI, 0.4-1.7) than MDI patients (i.e., 4.4 v. 3.4 hours); patients in both groups spent progressively less time on diabetes-related care by 1.2 minutes per week (95% CI, -1.7 to -0.7). Overall, mean time costs per person were $4600 with the SAPT group and $3523 with the MDI group (difference, $1077; 95% CI, $491-$1638). LIMITATIONS: Time spent on specific activities was not collected, and the estimates do not explicitly account for caregiver time associated with diabetes care activities. CONCLUSIONS: Patients receiving SAPT v. MDI spent approximately 2 hours more per week on diabetes-related care during pump initiation and 1 hour more per week thereafter, resulting in higher patient time costs.

Perspective: The case for research justice: inclusion of patients with limited English proficiency in clinical research.

Persons with limited English proficiency (LEP) constitute a growing portion of the U.S. population, yet they are underrepresented in clinical research. This inherently limits the societal benefits of the research and its generalizability to ethnic populations living in the United States. To illustrate the complexity associated with including LEP participants in clinical research, the authors critically evaluated LEP consent requirements posted on the Web sites of 134 academic health centers in March 2008. They found wide variability with regard to consent policies and striking interinstitutional differences in posted IRB policies and attitudes toward consent of LEP patients in research. The authors argue this variation highlights competing concerns between autonomy and justice. Outcomes-based justice requires inclusion of LEP patients in the research, yet the consent process is often resource-intensive and complex. The authors suggest that more uniform and specific guidance from federal agencies for enrollment of LEP patients in clinical research be established and that this guidance explicitly recalibrate the current balance between autonomy and justice. Investigators and institutional review boards should also develop streamlined best practices to reduce unnecessary effort and expense associated with recruitment of LEP individuals. LEP individuals should have fair access to clinical research in order to fully realize individual and societal benefits of their participation and to ensure the generalizability of scientific discovery.

Commentary: Per capita payments in clinical trials: reasonable costs versus bounty hunting.

Paying more for clinical research than the cost of doing the work may create a conflict of interest that could lead to overzealous recruitment, putting participants and scientific integrity at risk. Thus, although various policies prohibit "finder's fees" simply for recruiting patients, paying the actual costs for research is permissible. Whereas industry-sponsored research routinely pays for the costs of each patient enrolled, the line between reasonable and excessive costs merits more attention. In academic medical centers (AMCs), institutional review boards and conflict of interest committees usually are not involved in reviewing research budgets to determine whether per capita payments are excessive. Also, the costs for clinical services in research are not standardized. Instead, budgets are negotiated both internally, among departments within research institutions, and externally, between researchers and sponsors. Sometimes, rates paid by sponsors exceed what researchers usually receive or are actually paid for particular services, generating a surplus. Nevertheless, the authors see only limited cause for concern because, at the AMCs with which the authors are familiar, any monetary surplus generally remains within the research enterprise to cover unanticipated budget shortfalls or to support research staff in the future during lean times. In addition, the surplus from research budgets is not shared directly with individual investigators. However, further investigation is needed to determine whether practices outside AMCs pose greater concerns.

Developing a simplified consent form for biobanking.

BACKGROUND: Consent forms have lengthened over time and become harder for participants to understand. We sought to demonstrate the feasibility of creating a simplified consent form for biobanking that comprises the minimum information necessary to meet ethical and regulatory requirements. We then gathered preliminary data concerning its content from hypothetical biobank participants. METHODOLOGY/PRINCIPAL FINDINGS: We followed basic principles of plain-language writing and incorporated into a 2-page form (not including the signature page) those elements of information required by federal regulations and recommended by best practice guidelines for biobanking. We then recruited diabetes patients from community-based practices and randomized half (n = 56) to read the 2-page form, first on paper and then a second time on a tablet computer. Participants were encouraged to use "More information" buttons on the electronic version whenever they had questions or desired further information. These buttons led to a series of "Frequently Asked Questions" (FAQs) that contained additional detailed information. Participants were asked to identify specific sentences in the FAQs they thought would be important if they were considering taking part in a biorepository. On average, participants identified 7 FAQ sentences as important (mean 6.6, SD 14.7, range: 0-71). No one sentence was highlighted by a majority of participants; further, 34 (60.7%) participants did not highlight any FAQ sentences. CONCLUSIONS: Our preliminary findings suggest that our 2-page form contains the information that most prospective participants identify as important. Combining simplified forms with supplemental material for those participants who desire more information could help minimize consent form length and complexity, allowing the most substantively material information to be better highlighted and enabling potential participants to read the form and ask questions more effectively.

Patient reactions to confidentiality, liability, and financial aspects of informed consent in cardiology research.

BACKGROUND: Although the informed consent process is supposed to help potential research participants make informed and voluntary decisions about participating in research, little is known about how participants react to language in the informed consent document and whether their reactions are related to their willingness to enroll in clinical trials. We examined the relationship between patients' reactions to standard informed consent language and their willingness to participate in a hypothetical clinical trial. METHODS AND RESULTS: We simulated the consent process for a hypothetical cardiology clinical trial with 470 patients in an outpatient cardiovascular medicine clinic at a large academic medical center. We analyzed the spontaneous comments and questions that participants made during the interviews about each section of the informed consent document. Few participants made positive comments. Participants made the most negative comments about the sections on risks, study purpose or protocol, and payment for injury. Having a negative reaction to any section was associated with a lower likelihood of participating in the clinical trial. Using a multivariable model, we found that negative reactions in the patient rights, financial disclosure, and confidentiality sections predicted willingness to participate (P<0.001). CONCLUSIONS: Recognizing elements of informed consent that elicit questions and concerns from potential research participants may help investigators design clinical research trials and model language in a way that reduces concerns or increases participant understanding, thereby enhancing informed consent for research.

Oversight of financial conflicts of interest in commercially sponsored research in academic and nonacademic settings.

BACKGROUND: Studies of conflicts of interest in clinical research have focused on academic centers, but most clinical research takes place in nonacademic settings. OBJECTIVE: To compare oversight and management of investigators' financial relationships in academic and nonacademic research settings. DESIGN, SETTING, AND PARTICIPANTS: Survey of officials at 199 sites that contributed participants to commercially sponsored phase 3 clinical trials published in JAMA or the New England Journal of Medicine in 2006 and 2007. MEASUREMENTS AND MAIN RESULTS: Response rates were 66% for academic medical centers, 37% for nonacademic medical centers (inpatient), and 27% for outpatient nonacademic sites. Almost all academic medical centers (97%) and most nonacademic medical centers (87%) followed written conflict-of-interest policies, whereas 44% of outpatient nonacademic sites had written policies (P < 0.001). Academic and nonacademic medical centers relied mainly on internal institutional review boards (69% and 71%, respectively); outpatient nonacademic sites relied primarily on independent institutional review boards (59%; P < 0.001). CONCLUSIONS: Nonacademic sites have substantially different approaches to the oversight and management of financial relationships in commercially sponsored clinical research than academic medical centers. These differences warrant more attention to how financial relationships are monitored in community research settings.

Outcomes, health policy, and managed care: relationships between patient-reported outcome measures and clinical measures in outpatients with heart failure.

BACKGROUND: Patient-reported outcomes are increasingly used to assess the efficacy of new treatments. Understanding relationships between these and clinical measures can facilitate their interpretation. We examined associations between patient-reported measures of health-related quality of life and clinical indicators of disease severity in a large, heterogeneous sample of patients with heart failure. METHODS: Patient-reported measures, including the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the EuroQol Visual Analog Scale (VAS), and clinical measures, including peak VO(2), 6-minute walk distance, and New York Heart Association (NYHA) class, were assessed at baseline in 2331 patients with heart failure. We used general linear models to regress patient-reported measures on each clinical measure. Final models included for significant sociodemographic variables and 2-way interactions. RESULTS: The KCCQ was correlated with peak VO(2) (r = .21) and 6-minute walk distance (r = .27). The VAS was correlated with peak VO(2) (r = .09) and 6-minute walk distance (r = .11). Using the KCCQ as the response variable, a 1-SD difference in peak Vo(2) (4.7 mL/kg/min) was associated with a 2.86-point difference in the VAS (95% CI, 1.98-3.74) and a 4.75-point difference in the KCCQ (95% CI, 3.78-5.72). A 1-SD difference in 6-minute walk distance (105 m) was associated with a 2.78-point difference in the VAS (95% CI, 1.92-3.64) and a 5.92-point difference in the KCCQ (95% CI, 4.98-6.87); NYHA class III was associated with an 8.26-point lower VAS (95% CI, 6.59-9.93) and a 12.73-point lower KCCQ (95% CI, 10.92-14.53) than NYHA class II. CONCLUSIONS: These data may inform deliberations about how to best measure benefits of heart failure interventions, and they generally support the practice of considering a 5-point difference on the KCCQ and a 3-point difference on the VAS to be clinically meaningful.