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When participants enrolled in an HIV prevention trial hold a preventive misconception (PM) - expectations that experimental interventions will confer protection from HIV infection - they may engage in behaviors that increase their risk of acquiring HIV. This can raise ethical concerns about whether those enrolled in the trial understand the nature of participation and their safety. Consequently, we systematically evaluated the prevalence of PM and its association with risk behaviors in a trial examining three candidate regimens for oral HIV pre-exposure prophylaxis in which all participants received at least one antiretroviral agent. Overall, trial participants exhibited relatively high preventive expectations that may be associated with an increase in risk behaviors among men who have sex with men. In addition, we identified substantial site variability in PM that necessitates future research to uncover its source. This will allow appropriate measures to be taken to mitigate PM and help ensure that participants have an accurate understanding of the potential risks and benefits of trial participation throughout the course of a trial.

Purpose: Successful patient-focused drug development involves selecting and measuring outcomes in clinical trials that are important to patients. The U.S. Food & Drug Administration's definition of clinical benefit includes how patients feel, function, or survive. Patients are considered the experts in describing how they feel and function. In cancer trials, patient-reported measures of physical function provide insight into how patients function at baseline, benefit from the interventions being studied, and the impact of treatment side effects. We conducted a qualitative study with adults diagnosed with cancer to describe facets of physical function from their perspective and to identify which facets are most important to this patient population., Methods: Using concept elicitation and cognitive interviewing techniques, we conducted semi-structured interviews with 72 adults ≥ 22 years of age with cancer who received treatment with an anticancer drug or biologic within six months of the interview. We selected participants using purposive sampling with the aim to elicit diverse experiences regarding how they may interpret and respond to questions related to physical function. Participants were presented with patient-reported outcome (PRO) items representative of PRO measures used in cancer and general populations., Results: Five facets of how physical function relates to activities were defined from the patient perspective: ability, difficulty, limitation, satisfaction, and completion. More than half of the participants indicated that ability was the most important facet of physical function. The next most important were satisfaction (18.3%), limitation (14.1%), difficulty (5.6%), and completion (2.8%)., Conclusion: This study demonstrates that we must be more specific about the facets of physical function that we set out to assess when we use PRO measures to describe the patient experience. These results have implications for the specificity of physical function facets when measured in cancer clinical trials., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In contrast to traditional randomized controlled trials, embedded pragmatic clinical trials (ePCTs) are conducted within healthcare settings with real-world patient populations. ePCTs are intentionally designed to align with health system priorities leveraging existing healthcare system infrastructure and resources to ease intervention implementation and increase the likelihood that effective interventions translate into routine practice following the trial. The NIH Pragmatic Trials Collaboratory, funded by the National Institutes of Health (NIH), supports the conduct of large-scale ePCT Demonstration Projects that address major public health issues within healthcare systems. The Collaboratory has a unique opportunity to draw on the Demonstration Project experiences to generate lessons learned related to ePCTs and the dissemination and implementation of interventions tested in ePCTs. In this article, we use case studies from six completed Demonstration Projects to summarize the Collaboratory's experience with post-trial interpretation of results, and implications for sustainment (or de-implementation) of tested interventions. We highlight three key lessons learned. First, ineffective interventions (i.e., ePCT is null for the primary outcome) may be sustained if they have other measured benefits (e.g., secondary outcome or subgroup) or even perceived benefits (e.g., staff like the intervention). Second, effective interventions-even those solicited by the health system and/or designed with significant health system partner buy-in-may not be sustained if they require significant resources. Third, alignment with policy incentives is essential for achieving sustainment and scale-up of effective interventions. Our experiences point to several recommendations to aid in considering post-trial sustainment or de-implementation of interventions tested in ePCTs: (1) include secondary outcome measures that are salient to health system partners; (2) collect all appropriate data to allow for post hoc analysis of subgroups; (3) collect experience data from clinicians and staff; (4) engage policy-makers before starting the trial., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Background: Conducting an embedded pragmatic clinical trial in the workflow of a healthcare system is a complex endeavor. The complexity of the intervention delivery can have implications for study planning, ability to maintain fidelity to the intervention during the trial, and/or ability to detect meaningful differences in outcomes., Methods: We conducted a literature review, developed a tool, and conducted two rounds of phone calls with NIH Pragmatic Trials Collaboratory Demonstration Project principal investigators to develop the Intervention Delivery Complexity Tool. After refining the tool, we piloted it with Collaboratory demonstration projects and developed an online version of the tool using the R Shiny application (https://duke-som.shinyapps.io/ICT-ePCT/)., Results: The 6-item tool consists of internal and external factors. Internal factors pertain to the intervention itself and include workflow, training, and the number of intervention components. External factors are related to intervention delivery at the system level including differences in healthcare systems, the dependency on setting for implementation, and the number of steps between the intervention and the outcome., Conclusion: The Intervention Delivery Complexity Tool was developed as a standard way to overcome communication challenges of intervention delivery within an embedded pragmatic trial. This version of the tool is most likely to be useful to the trial team and its health system partners during trial planning and conduct. We expect further evolution of the tool as more pragmatic trials are conducted and feedback is received on its performance outside of the NIH Pragmatic Trials Collaboratory., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The Patient-Reported Outcomes Measurement Information System (PROMIS®) Sexual Function and Satisfaction (SexFS) version 2.0 measurement tool was developed to assess sexual functioning and satisfaction in the general population regardless of health condition and sexual orientation., Aim: The study aimed to evaluate the psychometric properties of the Swedish version of the PROMIS SexFS measure in clinical and nonclinical populations of young adults (aged <40 years)., Methods: The SexFS was answered by a clinical population of young adult women ( n  = 180) and men ( n  = 110) with breast cancer and testicular cancer, respectively, and a nonclinical population of young adult women ( n  = 511) and men ( n  = 324) from the general population. Psychometric properties were evaluated by examining data quality (score distribution, floor and ceiling effects, proportion of missing data), construct validity (corrected item, total correlation, scaling success), and reliability (Cronbach α)., Outcomes: The following domains of the SexFS 2.0 were investigated: Vaginal Lubrication, Vaginal Discomfort, Vulvar Discomfort- Clitoral, Vulvar Discomfort- Labial, Erectile Function, Interest in Sexual Activity, Satisfaction With Sex Life, Orgasm- Ability, and Orgasm- Pleasure., Results: The Swedish version of the SexFS 2.0 generated data of acceptable quality. Some noteworthy floor or ceiling effects were identified across domains and respondent groups. Corrected item totals were used to express the coherence between an item and the other items in the domain. The correlation coefficients were above 0.40 for all items, except for 1 of the items within the Vaginal Discomfort domain and for the items in the Erectile Function domain in the nonclinical group of men. High proportions of scaling success were noted across domains (96%-100%). Reliability was satisfactory (α = 0.74-0.92) for all domains, expect for Erectile Function of the nonclinical group (α = 0.53), due to low variability in item responses, which was improved somewhat (α = 0.65) when combined with the clinical group., Clinical Implications: A flexible tool to measure self-reported sexual function and satisfaction in young men and women is available for researchers and clinicians in Sweden., Strengths and Limitations: The nationwide population-based sample of patients with cancer, identified from national quality registers, minimized selection bias. However, men in the general population had a lower response rate (34%) compared to the other groups, which introduced a risk of bias in estimates. The psychometric evaluation was limited to young adults (aged 19-40 years)., Conclusion: The results provide evidence for the validity and reliability of the Swedish version of the SexFS measure for the assessment of sexual functioning and satisfaction in young adults from both clinical and nonclinical populations., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

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., (© The Author(s) 2022.)

Purpose: Bladder diaries are a key source of information about lower urinary tract symptoms (LUTS); however, many patients do not complete them as instructed. Questionnaire-based patient-reported outcome measures (PROMs) are another option for reporting LUTS but may have recall bias. We assessed the strength of the associations between PROMs and a 3-day bladder diary., Materials and Methods: Symptomatic adults from 6 tertiary care sites completed a 3-day paper bladder diary and 3-, 7-, and 30-day electronic PROMs. We assessed the linear associations between mapped pairs of diary variables and responses to PROM items using biserial and polyserial correlation coefficients with 95% confidence intervals., Results: Of 290 enrolled participants, 175 (60%) completed the bladder diary as instructed and at least one corresponding PROM. Linear associations were strongest between the diary and 3-day recall of daytime frequency (r = 0.75) and nighttime frequency (r = 0.69), followed by voids with urgency sensations (r = 0.62), and an item reporting any incontinence (r = 0.56). Linear associations between bladder diary and specific incontinence variables (e.g., stress, urgency) were low to negligible (ranging from r = 0.16-0.39). Linear associations were consistent across the 3-, 7-, and 30-day recall periods., Conclusions: Missing and unusable bladder diary data were common, highlighting the patient burden associated with this method of data collection. A questionnaire-based PROM is a reasonable alternative to a diary for reporting voiding frequency and may offer an easier option for reporting some symptoms., (© 2022 Wiley Periodicals LLC.)

For patients with optimally treated chronic myeloid leukemia (CML), discontinuation of tyrosine kinase inhibitor (TKI) therapy can lead to treatment-free remission. In previous trials, TKI discontinuation has been associated with increased musculoskeletal pain in some patients ("withdrawal syndrome"), based on physician-reported adverse events (AE). Patient-reported pain has not been described. The Life After Stopping TKI study was a 14-site prospective, non-randomized clinical trial of TKI discontinuation. We defined increased pain after discontinuation as: (i) a physician-reported pain AE, (ii) a 2-level increase in self-reported musculoskeletal pain (4-level single item), or (iii) initiation of a medication for pain. We plotted the trajectory of patient-reported pain over time using a piecewise mixed-effects ordinal logistic model. Within 3 months of discontinuation, 35 of 172 patients (20.3%) had a physician-reported pain AE, 22 of 172 (12.8%) had an increase in self-reported pain, and 18 of 154 (11.7%) initiated a pain medication. Agreement among these measures was limited; overall, 60 of 172 patients (34.9%) had increased pain. Three patients (1.7%) restarted a TKI because of pain. The modelpredicted trajectory showed an increase in pain in the first 3 months followed by a decrease, returning to baseline levels by 6 months and further decreasing after that. This trajectory was similar among patients who did and did not restart TKI, suggesting that resuming a TKI for withdrawal syndrome may be necessary for some, but other approaches to manage pain should be tried so that patients can remain in treatment-free remission when possible.

Importance: Communication during conversations about death is critical; however, little is known about the language clinicians and families use to discuss death., Objective: To characterize (1) the way death is discussed in family meetings between parents of critically ill infants and the clinical team and (2) how discussion of death differs between clinicians and family members., Design, Setting, and Participants: This longitudinal qualitative study took place at a single academic hospital in the southeast US. Patients were enrolled from September 2018 to September 2020, and infants were followed up longitudinally throughout their hospitalization. Participants included families of infants with neurologic conditions who were hospitalized in the intensive care unit and had a planned family meeting to discuss neurologic prognosis or starting, not starting, or discontinuing life-sustaining treatment. Family meetings were recorded, transcribed, and deidentified before being screened for discussion of death., Main Outcomes and Measures: The main outcome was the language used to reference death during family meetings between parents and clinicians. Conventional content analysis was used to analyze data., Results: A total of 68 family meetings involving 36 parents of 24 infants were screened; 33 family meetings (49%) involving 20 parents (56%) and 13 infants (54%) included discussion of death. Most parents involved in discussion of death identified as the infant's mother (13 [65%]) and as Black (12 [60%]). Death was referenced 406 times throughout the family meetings (275 times by clinicians and 131 times by family members); the words die, death, dying, or stillborn were used 5% of the time by clinicians (13 of 275 references) and 15% of the time by family members (19 of 131 references). Four types of euphemisms used in place of die, death, dying, or stillborn were identified: (1) survival framing (eg, not live), (2) colloquialisms (eg, pass away), (3) medical jargon, including obscure technical terms (eg, code event) or talking around death with physiologic terms (eg, irrecoverable heart rate drop), and (4) pronouns without an antecedent (eg, it). The most common type of euphemism used by clinicians was medical jargon (118 of 275 references [43%]). The most common type of euphemism used by family members was colloquialism (44 of 131 references [34%])., Conclusions and Relevance: In this qualitative study, the words die, death, dying, or stillborn were rarely used to refer to death in family meetings with clinicians. Families most often used colloquialisms to reference death, and clinicians most often used medical jargon. Future work should evaluate the effects of euphemisms on mutual understanding, shared decision-making, and clinician-family relationships.

Objective: To characterize decisional satisfaction, regret, and conflict among parents of critically ill infants with neurologic conditions., Study Design: In this prospective cohort study, we enrolled parents of infants with neurologic conditions in the intensive care unit (ICU). Hospital discharge surveys included the validated Family Satisfaction with the ICU (FS-ICU) decision making subscale, Decision Regret Scale (DRS), and Decisional Conflict Scale (DCS). We defined high satisfaction with decision making as an FS-ICU score ≥75, high decisional regret/conflict as DRS/DCS score >25, and within-couple disagreement as a difference of at least 25 points between scores., Results: We enrolled 61 parents of 40 infants (n = 40 mothers, n = 21 fathers); 35 mothers and 15 fathers completed surveys. Most mothers reported high satisfaction with decision making (27 of 35; 77%) and low decision regret (28 of 35; 80%); 40% (14 of 35) reported high decisional conflict. Mothers and fathers reported higher decisional conflict in the domains of uncertainty and values clarity compared with the domain of effective decision making (Bonferroni-corrected P < .05). There were no differences in decision outcomes between paired mothers and fathers; however, within any given couple, there were numerous instances of disagreement (7 of 15 for decision regret and 5 of 15 for decisional conflict)., Conclusions: Many parents experience decisional conflict even if they ultimately have high satisfaction and low regret, underscoring the need for decision aids targeting uncertainty and values clarity. Couples frequently experience different levels of decisional regret and conflict., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The COVID-19 pandemic has considerably disrupted nearly all aspects of daily life, including healthcare delivery and clinical research. Because pragmatic clinical trials are often embedded within healthcare delivery systems, they may be at high risk of disruption due to the dual impacts on the conduct of both care and research., Methods: We collected qualitative data using multiple methods to characterize the impact of COVID-19 on the research activities of 14 active pragmatic clinical trials in the National Institutes of Health (NIH) Health Care Systems Research Collaboratory. A COVID-19 impact questionnaire was administered electronically to principal investigators in June 2020. Text responses were analyzed thematically, and qualitative summaries were subsequently reviewed by five independent reviewers, who made iterative revisions. Additional COVID-19-related impacts were identified during virtual meetings with trial teams during April-July 2020 and combined with questionnaire responses for analysis., Results: Impacts of the pandemic were broadly classified into two main types: healthcare operations and social distancing. In some instances, trial delays created statistical challenges, particularly with trials using stepped-wedge designs, and necessitated changing data collection strategies or modifying interventions. The majority of projects used existing stakeholder-driven approaches to adapt interventions. Several benefits of these adaptions were identified, including expanded outreach capabilities and ability to study virtual intervention delivery. All trial teams were able to adapt to pandemic-related modifications., Conclusion: In a group of 14 ongoing pragmatic clinical trials, there was significant impact of COVID-19 on trial activities. Engaging appropriate stakeholders was critical to designing and implementing trial modifications and making continued safe progress toward meeting research objectives., (© 2022. The Author(s).)

Background: Sexual dysfunction is a common symptom of multiple sclerosis (MS). Clinically meaningful and psychometrically sound measures of sexual function validated in people with MS are necessary to identify people with MS who experience problems with sexual function., Aim: To evaluate the Patient-Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction (SexFS) v2.0 measure in people with MS and to extend the PROMIS SexFS Brief and Full Profiles to include additional aspects of sexual function relevant to people living with MS., Methods: A convenience sample of MS clinicians and sexually active individuals with MS ranked relevance of 26 items that listed specific factors that interfere with sexual function. Rankings were used to select items to include in the modified SexFS for Multiple Sclerosis (SexFS-MS) profiles. Sex-FS Brief and Full profiles along with the top 22 ranked interfering factor items underwent cognitive interviews (CI) to assess whether the items were understandable and meaningful., Outcomes: The SexFS as originally published functioned well in people with MS after minor modifications., Results: Twelve MS clinicians and 26 people with MS ranked items. The 10 highest ranked questions about factors that interfere with sexual function most relevant to people with MS were added to the SexFS-MS Brief profiles and 18 to the Full profiles. Ten men and 12 women with MS participated in CIs and found most items to be clear and meaningful. However, important changes were made to the profile instructions, some response sets, and to some items to improve clarity and function. New items to assess numbness and reasons why sexually active people choose at times not to engage in sexual activity were added., Clinical Implications: Brief and Full profiles are freely available and are recommended for research and clinical practice that include people with MS., Strengths & Limitations: This study is the first to provide validity evidence for the PROMIS SexFS in people living with MS. Though the PROMIS SexFS was tested in people who identify as lesbian, gay, or bisexual, only individuals who identified as heterosexual participated in this study. Results may not represent views of people with MS who identify as other sexual orientations who may have different concerns and priorities related to sexual function., Conclusion: This study extended the PROMIS SexFS Brief and Full profiles to create the SexFS-MS by adding items that measure most relevant issues related to sexual function in individuals living with MS. Amtmann D, Bamer AM, Salem R, et al. Extension and Evaluation of the PROMIS Sexual Function and Satisfaction Measures for Use in Adults Living With Multiple Sclerosis. J Sex Med 2022;19:719-728., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Collateral findings in pragmatic clinical trials are findings that may have implications for patients' health but were not generated to address a trial's primary research questions. It is uncertain how best to communicate these collateral findings to patients., Objectives: To determine how reactions to a letter communicating collateral findings relate to who signed the letter, the type of finding, or whether the letter specified that the finding arose from a pragmatic clinical trial., Research Design: Web-based survey experiment using a between-subjects design in which respondents were randomly assigned within education strata to view and respond to 1 of 16 hypothetical scenarios., Subjects: Adults recruited from an online panel constructed from a probability sample of US-based postal addresses., Measures: The primary outcomes were the action the respondent would take next (i.e., contact a doctor immediately or something else) and the respondent's emotional reactions (i.e., all positive, all negative, mixed, or none)., Results: A total of 4080 respondents had analyzable data. Although some effects were statistically significant (P < .05), none exceeded a prespecified threshold for policy relevance (15 or more percentage points). Ratings of letter clarity and level of understanding were lower for letters that included a description of the clinical trial., Conclusions: Signatory and level of detail about collateral findings did not substantially affect people's intentions to take the recommended action of contacting their doctor. Deciding whether to include a description of the pragmatic clinical trial requires a trade-off between transparency and more difficulty understanding the contents of the letter., (© 2021. Society of General Internal Medicine.)

Purpose: Patients diagnosed with ductal carcinoma in situ (DCIS) face trade-offs when deciding among different treatments, including surgery, radiation, and endocrine therapy. A less chosen option is active monitoring. While evidence from clinical trials is not yet available, observational studies show comparable results for active monitoring and immediate treatment on cancer outcomes in select subgroups of patients. We developed and tested a web-based decision support tool (DST) to help patients explore current knowledge about DCIS and make an informed choice., Methods: The DST, an interactive web application, was informed by literature reviews and formative work with patients, breast surgeons, and health communication experts. We conducted iterative interviews to evaluate the DST content among women with and without a history of breast cancer, as well as breast cancer experts. For usability testing, we conducted an online survey among women with and without a history of breast cancer., Results: For content evaluation, 5 women with and 10 women without a history of DCIS were interviewed. The sample included 11 White and 4 non-White women, with a mean age of 64 years. The expert sample consisted of 5 attendings and a physician assistant. The feedback was used to add, clarify, or reorganize information in the DST. For usability testing, 22 participants with a mean age of 61 years were recruited including 15 White and 7 Black women and 6 women with a history of DCIS. The mean usability score was 3.7 out of 5. Most participants (86%) found that the DST provided unbiased information about treatments. To improve usability, we reduced the per-page content and added navigation cues., Conclusion: Content and usability evaluation showed that the DST helps patients explore trade-offs of active monitoring and immediate treatment. By adopting a personalized approach, the tool will enable informed decisions aligned with patients' values and expectations., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Clinical trials that evaluate new medical products often use clinical outcome assessments to measure how patients feel or function. Determining the evidentiary support needed for clinical outcome assessments is challenging but necessary to ensure scores from a clinical outcome assessment reflect the relevant aspects of patients' health. Modern validity theory-from educational and psychological testing-addresses the challenge by requiring that investigators state key assumptions underlying the proposed use of a clinical outcome assessment and collect evidence for or against those assumptions., Methods: This article describes the argument-based approach to validity using an example of a performance outcome measure-the Multi-luminance Mobility Test-designed to assess patients with inherited retinal dystrophy that causes progressive loss of night vision. For the proposed interpretation and use of a performance outcome measure to be reasonable, several key assumptions need to be plausible. I describe the assumptions along with examples of supporting evidence from the published literature to evaluate each assumption within the rationale., Results: This article provides an example of a validity rationale to evaluate a clinical outcome assessment using the Multi-luminance Mobility Test as an example., Conclusion: The demonstration illustrates the use of the argument-based approach to validity evaluation and the challenges in supporting parts of a validity rationale for clinical outcome assessments that measure how patients feel and function in a more indirect way. By making clinical outcome assessment validation practices consistent with modern validity theory, investigators, sponsors, and regulators should be able to communicate more clearly and direct resources more efficiently to support the creation of patient-centered endpoints in clinical trials.

Background: Ethical responsibilities for monitoring and responding to signals of behavioral and mental health risk (such as suicidal ideation, opioid use disorder, or depression) in general clinical research have been described; however, pragmatic clinical trials (PCTs) raise new contextual challenges., Methods: We use our experience with the PRISM (Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing) program, which is a component of the Helping End Addiction Long-Term (HEAL) Initiative, to provide examples of research studying nonpharmacologic interventions for pain that collect sensitive data. Members of the PRISM Ethics and Regulatory Core and Patient-Centered Outcome Core Working Group discussed and refined considerations and recommendations., Results: PCT researchers can help identify the extent of their ethical obligations to monitor and respond to signals of potential behavioral and mental health risks by understanding and aligning stakeholder expectations; considering characteristics of the trial and study population; defining triggers, thresholds, and responsibilities for action; identifying appropriate response mechanisms and capabilities; integrating responses with health systems; and addressing privacy. Based on such an assessment, researchers should proactively identify if, when, and how a response will be triggered. Doing so necessitates that stakeholders understand their roles in managing such risks. Finally, consent forms and other study disclosures should clearly state what if any responses might be taken., Conclusion: Early and ongoing bi-directional communication with relevant stakeholders is critical to identifying and meeting the ethical challenges for PCTs when managing and responding to behavioral and mental health data that potentially signal elevated risk to individuals., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Treatment-free remission (TFR) is a goal for patients with chronic myeloid leukemia (CML). Functional outcomes after discontinuing tyrosine kinase inhibitor (TKI) treatment have not been described. Patient-Reported Outcomes Measurement Information System (PROMIS) measures of social, physical, cognitive, and sexual function were assessed over 36 months in 172 adult patients with chronic phase CML from 14 sites at baseline (on TKI) and after discontinuation. Linear mixed-effects models described the average trajectories for each patient-reported outcome measure after discontinuation and in those who restarted TKI. Of 112 patients in TFR at 12 months, 103 (92.0%) had a 3-point or greater improvement in social function, 80 (71.4%) in social isolation, 11 (9.8%) in satisfaction with sex life, 4 (3.6%) in physical function, and no patients had a 3-point or greater improvement in cognitive function or interest in sexual activity. Patients' scores worsened after restarting TKI. This novel information on functional outcomes in TFR can help guide patient and clinician decision making., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Tools for diagnosing sexual dysfunction and for tracking outcomes of interest include clinician interviews, physical exam, and patient self-report. Limited work has described relationships among these three sources of information regarding female sexual dysfunction and vulvovaginal health., Aim: We describe correlations among data collected from clinician interviews, clinical gynecological examination, and patient self-report., Methods: Data are from a single-site, single-arm, prospective trial in 100 postmenopausal patients with a history of breast or endometrial cancer who sought treatment for vulvovaginal symptoms. The trial collected a standardized clinical gynecologic exam, clinician-reported outcome (ClinRO) measures of vulvovaginal dryness and pain, and patient-reported outcome (PRO) measures of sexual function, including PROMIS Sexual Function and Satisfaction (SexFS) lubrication, vaginal discomfort, labial discomfort, and clitoral discomfort and Female Sexual Function Index (FSFI) lubrication and pain. We examined polyserial correlations between measures with bootstrapped 95% confidence intervals from the baseline and 12-14-week timepoints., Results: All of the relationships between the ClinRO variables and the PRO variables were in the expected direction (ie, positive), but the strength of the relationships varied substantially. At 12-14 weeks, there were medium-to-large correlations between ClinRO vaginal dryness and SexFS Lubrication (0.64), ClinRO vulvar dryness and SexFS Lubrication (0.46), ClinRO vulvar discomfort and SexFS Labial Discomfort (0.70), and ClinRO vulvar discomfort and SexFS Clitoral Discomfort (0.43). With one exception, the correlations between the exam variables and the corresponding PRO scores were small (range 0.01-0.27)., Strengths & Limitations: Our study included a comprehensive, standardized gynecologic exam designed specifically to evaluate sexual dysfunction as well as established PRO measures with significant evidence for validity. A limitation of our findings is that the sample size was relatively small, and our sample was restricted to women who received cancer treatments known to have dramatic effects on vulvovaginal tissue quality., Conclusion: Patient- and clinician-reported vulvovaginal dryness and discomfort were moderately correlated with each other but not with clinical gynecologic exam findings. Understanding the relationships among these different types of data highlights the distinct contributions of each to understand vulvovaginal tissue quality and patient sexual function after cancer. Flynn KE, Lin L, Carter J, et al. Correspondence Between Clinician Ratings of Vulvovaginal Health and Patient-Reported Sexual Function After Cancer. J Sex Med 2021;18:1768-1774., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

The past 100 years have witnessed an evolution of the meaning of validity and validation within the fields of education and psychology. Validity was once viewed as a property of tests and scales, but is now viewed as the extent to which theory and evidence support proposed interpretations and uses of test scores. Uncertainty about what types of validity evidence were needed motivated the current "argument-based" approach, as reflected in the 2014 Standards for Educational and Psychological Testing. According to this approach, investigators should delineate the assumptions required in order for a proposed interpretation or use to be plausible and then seek evidence that supports or refutes those assumptions. Though validation practices within the field of patient-reported outcome measurement have implicitly included many elements of the argument-based approach, the approach has yet to be explicitly adopted. To facilitate adoption, this article proposes an initial set of assumptions that might be included in most arguments for research-related interpretations and uses of scores from patient-reported outcome measures. The article also includes brief descriptions of the types of evidence that would be best suited for evaluating each assumption. It is hoped that these generic assumptions will stimulate further discussion and debate among quality of life researchers regarding how best to adopt modern validity theory to patient-reported outcome measures.

Objective: To explore the perspectives of normal bladder function among women with lower urinary tract symptoms., Methods: This was a secondary analysis of qualitative data from structured interviews with 50 adult women with lower urinary tract symptoms. A directed content analysis of the transcripts explored women's perspectives on normal bladder function., Results: Participants' descriptions of "normal" took many forms and were based on several aspects of bladder function. A prominent feature of normal was that voiding occurred as a seamless process, beginning with an urge sensation, followed by voiding with ease and to completion, and then "being done." Descriptions of normal were based largely on concepts of voiding regularity, including voiding frequency, intervals, and patterns during the day and night. Another aspect of normal bladder function was the notion of having control in terms of not leaking urine, as well as the ability to hold urine and defer urination. Views of normal bladder function extended to the absence of symptoms and the impact of being symptom-free on day-to-day life, including not having to think about or worry about the bladder or limit daily activities., Conclusion: Women's perspectives on normal bladder function are multifaceted, reflecting attributes most salient to each individual and likely informed by their personal experience with symptoms and their influence on daily life. This work has implications for how clinicians might engage women in discussing bladder symptoms and can inform future research and public health messaging about normal bladder function., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

Aims: Bother attributed to lower urinary tract symptoms (LUTS) drives care-seeking and treatment aggressiveness. The longitudinal relationship of LUTS severity and bother in a care-seeking cohort, however, is not well understood. We aim to conduct a longitudinal evaluation of LUTS severity and bother and identify characteristics of patients with discordant LUTS bother relative to severity., Methods: Men and women with LUTS seeking care at six US tertiary care centers enrolled in the symptoms of lower urinary tract dysfunction research network study. Patients reporting at least one urinary symptom based on the LUTS Tool were prospectively enrolled from June 2015 to January 2017. Correlations were used to assess the relationship between LUTS severity and bother. Discordance scores (ie, the difference between bother and severity) were used to classify patients with high and low bother. Patients were classified as having high or low bother phenotypes if scores were one standard deviation above or below zero, respectively. Repeated measures multinomial logistic regression evaluated characteristics associated with high and low bother phenotypes., Results: LUTS severity and bother were at least moderately correlated for all symptom items and highly correlated for 13 out of 21 items. Correlations were highest for urgency, and lowest for daytime frequency and urinary incontinence. Odds of being in high bother phenotype were lowest at 3 and 12 months (3 months vs baseline odds ratio [OR] = 0.71, 95% confidence ninterval [CI] = 0.54-0.94; 12 months vs baseline OR = 0.66, 95% CI = 0.48-0.91), and highest for those who endorsed all urgency questions (OR = 3.65, 95% CI = 2.17-6.13). Odds of being in the low bother phenotype were lowest for patients who endorsed all urgency items (OR = 0.33, 95% CI = 0.26-0.42), and all frequency items (OR = 0.68, 95% CI = 0.53-0.88)., Conclusions: LUTS severity and bother correlate highly and measurement of both in clinical practice is likely redundant. There are patient factors associated with discordance which may justify additional evaluation., (© 2020 Wiley Periodicals LLC.)

Patient-reported health data provide information for pragmatic clinical trials that may not be readily available from electronic health records or administrative claims data. In this report, we present key considerations for collecting patient-reported health information in pragmatic clinical trials, which are informed by best practices from patient-reported outcome research. We focus on question design and administration via electronic data collection platforms with respect to 3 types of patient-reported health data: medication use, utilization of health care services, and comorbid conditions. We summarize key scientific literature on the accuracy of these patient-reported data compared with electronic health record data. We discuss question design in detail, specifically defining the concept to be measured, patient understanding of the concept, recall periods of the question, and patient willingness to report. In addition, we discuss approaches for question administration and data collection platforms, which are key aspects of successful patient-reported data collection., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: Measurement of self-reported lower urinary tract symptoms (LUTS) typically uses a recall period, for example, "In the past 30 days…." Compared to averaged daily reports, 30-day recall is generally unbiased, but recall bias varies by item. We examined the associations between personal characteristics (eg, age, symptom bother) and 30-day recall of LUTS using items from the Symptoms of Lower Urinary Tract Dysfunction Research Network Comprehensive Assessment of Self-reported Urinary Symptoms questionnaire., Methods: Participants (127 women and 127 men) were recruited from 6 US tertiary care sites. They completed daily assessments for 30 days and a 30-day recall assessment at the end of the study month. For each of the 18 tested items, representing 10 LUTS, the average of the participant's daily responses was modeled as a function of their 30-day recall, the personal characteristic, and the interaction between the 30-day recall and the characteristic in separate general linear regression models, adjusted for sex., Results: Nine items representing 7 LUTS exhibited under- or overreporting (recall bias) for at least 25% of participants. Bias was associated with personal characteristics for six LUTS. Underreporting of incontinence was associated with older age, lower anxiety, and negative affect; overreporting of other LUTS was associated with, symptom bother, symptom variability, anxiety, and depression., Conclusions: We identified under- or overreporting that was associated with personal characteristics for six common LUTS. Some cues (eg, less bother and lower anxiety) were related to recall bias in an unexpected direction. Thus, providers should exercise caution when making judgments about the accuracy of a patient's symptom recall based on patient demographic and psychosocial characteristics., (© 2020 Wiley Periodicals LLC.)

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.

Patient-reported outcome measures (PROMs) are frequently used in research to reflect the patient's perspective. In this commentary, I argue that further improvements can be made in how we develop and evaluate PROMs by viewing assessment as a type of conversation. Philosophically speaking, a PROM assessment can be conceptualized as a formal conversation that serves as a model of an informal, longer, and more nuanced conversation with a research participant about their health experience. Psychologically speaking, evidence from research in survey methodology and discursive psychology shows that respondents to self-report measures behave in ways consistent with the idea that they are doing their best to participate in a conversation, albeit an unusual one. Several suggestions are offered for creating a better conversational context through study materials and PROM instructions, and by improving the yield of cognitive interviews. It is hoped that this commentary can stimulate further discussions in our field regarding how to integrate insights about the conversational nature of assessment from survey research and discursive psychology to better reflect the patient's voice in research.

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.

Background: Limited patient-provider communication about sexual health is a crucial barrier to patients receiving treatment for sexual problems, and little is known about how patient sexual orientation is associated with patient-provider communication about sexual problems., Objective: To describe the prevalence of patient-provider communication about sexual problems and the associations between communication and (1) persistent sexual problems and (2) whether those who identified as lesbian, gay, or bisexual had disclosed their sexual orientation to their clinicians., Design: Cross-sectional, online survey PARTICIPANTS: 4325 English-speaking US adults from KnowledgePanel®, a probability-based sample of the civilian, noninstitutionalized population., Main Measures: Sexual orientation, disclosure of sexual orientation (being "out") to a health care provider, communication with health care providers regarding sexual problems or concerns, and persistent sexual problems or concerns., Key Results: In the past year, 8-15% of US adults discussed a sexual problem or concern with a health care provider. Between 23 and 42% of US adults reported persistent sexual problem(s) in the past year, and of those, 18% of gay/lesbian women, 20% of heterosexual women, 22% of bisexual women, 30% of gay men, 31% of heterosexual men, and 37% of bisexual men had discussed a sexual concern with a clinician. Eighty percent of gay/lesbian women and 70% of gay men had disclosed their sexual orientation to their regular health care provider, versus only 24% of bisexual men and women. Among those who were "out," 30% had ever talked to a clinician about a sexual problem compared with 17% of those who were not "out." A smaller proportion of lesbian women had ever received care or treatment for a sexual problem, 6% compared with 14-23% in the other groups., Conclusions: There are significant unmet needs among US adults with regard to patient-provider communication about sexual problems or concerns. Improving patient-provider communication about sexual health is critical.

Purpose: Self-reported measurement tools often provide a recall period, eg "In the past 7 days…" For lower urinary tract symptoms the concordance of end of day (daily) reports with 7 and 30-day recalled reports is unknown to our knowledge. We evaluated how accurately 7 or 30-day recall questions capture lower urinary tract symptoms., Materials and Methods: The 261 female and 254 male participants were recruited from a total of 6 United States tertiary care sites. We evaluated 18 items representing 7 symptoms covering storage, voiding and post-micturition symptoms. Item responses on the daily forms were averaged for a 7 or a 30-day period and compared to the corresponding 7 or 30-day recall version of the item. Analyses were item and gender specific. Within person concordance was assessed using the Pearson correlation. Bias (systematic overreporting or underreporting) was calculated as the difference between the recalled item and the averaged daily item score, and reported as a percent of the item scale., Results: All correlations exceeded 0.60. Correlations between averaged daily reports and recalled reports ranged from 0.72 to 0.89 for 7 days and from 0.71 to 0.91 for 30 days among women, and from 0.68 to 0.90 and 0.68 to 0.95, respectively, among men. Most items did not show systematic bias and the median percent bias did not exceed 10% for any item. However, bias exceeding ±10% for some items was observed in a subset of individuals., Conclusions: Recalled reports during the 7 and 30 days tracked well with averaged daily reports for men and women. Systematic bias was minimal, suggesting that 7 and 30-day recall periods for self-reported lower urinary tract symptoms are reasonable.

Purpose: Some patients continue to have bothersome lower urinary tract symptoms despite treatment. We examined characteristics associated with bother from lower urinary tract symptoms in a prospective cohort., Materials and Methods: In this 1-year prospective, observational cohort study we obtained data on patients with lower urinary tract symptoms who were seeking care at a total of 6 tertiary care centers in the United States. Participants answered the AUA-SI (American Urological Association Symptom Index) global urinary bother question at study entry and 12 months later. Multilevel logistic and linear regression was used to identify factors associated with worsening bother and bother at 12 months, respectively., Results: Of the 756 participants 121 (16%) had worsened lower urinary tract symptom bother during the study period. When adjusted for other variables, worsened lower urinary tract symptom bother was more likely among men who were nonwhite (OR 1.79, 95% CI 0.94-3.40) or who had diabetes (OR 1.68, 95% CI 0.86-3.27) and among women with diabetes (OR 1.77, 95% CI 0.85-3.67), prior treatment of lower urinary tract symptoms (OR 2.58, 95% CI 1.22-5.46) or a higher depression level (OR 1.29, 95% CI 1.10-1.52). Baseline factors associated with more severe bother at 12 months in men included more severe bother at baseline, nonwhite race, worse urinary frequency and incontinence, and higher levels of stress (p <0.05). Among women more severe bother at baseline, urinary urgency and frequency, and worse physical function were associated with more severe bother at 12 months., Conclusions: Urinary symptom severity at baseline, race, depression and psychological stress were associated with the bother of lower urinary tract symptoms in a prospective cohort of men and women treated at tertiary care facilities. These findings may inform the clinical care of patients with bothersome lower urinary tract symptoms and direct providers to better prognosticate for patients with challenging lower urinary tract symptoms cases.

Aims: To develop a representative, self-report assessment of lower urinary tract symptoms (LUTS) for men and women, the symptoms of Lower Urinary Tract Dysfunction Research Network Symptom Index-29 (LURN SI-29)., Methods: Women and men seeking treatment for LUTS at one of six academic medical centers in the US were assessed at baseline, 3-month and 12-month intervals. Twelve-month data on 78 LURN SI-29 items were analyzed among 353 women and 420 men using exploratory factor analysis (EFA), with factor structure confirmed using confirmatory factor analysis (CFA). Internal consistency, reliability, and validity of the five developed scales were evaluated by assessing correlations with the American Urological Association Symptom Index (AUA-SI), the genitourinary pain index (GUPI), and the Pelvic Floor Distress Inventory-20 (PFDI-20), and by examining expected sex differences in scores., Results: EFA results (n = 150 women; 150 men) produced an interpretable eight-factor solution, with three of the factors comprised of dichotomous items addressing LUTS-associated sensations. The remaining five factors, confirmed with CFA in an independent sample of 473 participants, produced five scales: incontinence, urgency, voiding difficulty, bladder pain, and nocturia. Subscales and total LURN SI-29 scores were correlated as expected with AUA-SI, GUPI, and PFDI-20. LURN SI-29 scores also performed as expected in differentiating men from women based upon clinically expected differences, with men reporting more voiding difficulties and nocturia, and women reporting more urgency and incontinence., Conclusions: The LURN SI-29 questionnaire has the potential to improve research and clinical outcome measurement for both men and women with LUTS., (© 2019 Wiley Periodicals, Inc.)

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.

Data documenting poor understanding among research participants and real-time efforts to assess comprehension in large-scale studies are focusing new attention on informed consent comprehension. Within the context of biobanking consent, we previously convened a multidisciplinary panel to reach consensus about what information must be understood for a prospective participant's consent to be considered valid. Subsequently, we presented them with data from another study showing that many U.S. adults would fail to comprehend the information the panel had deemed essential. When asked to evaluate the importance of the information again, panelists' opinions shifted dramatically in the direction of requiring that less information be understood. Follow-up interviews indicated significant uncertainty about defining a threshold of understanding and what should happen when prospective participants are unable to grasp key information. These findings have important implications for urgently needed discussion of whether consent comprehension is an ethical requirement or an ethical aspiration.

Background: Some HIV prevention research participants may hold a "preventive misconception" (PM), an overestimate of the probability or level of personal protection afforded by trial participation. However, these reports typically rely upon small, retrospective qualitative assessments that did not use a standardized approach., Methods: We administered a measure of PM called PREMIS, during Microbicide Trials Network 020-A Study to Prevent Infection with a Ring for Extended Use, a large, multicenter, placebo-controlled, phase III trial evaluating the safety and efficacy of a dapivirine vaginal ring among women at risk for HIV infection in Malawi, South Africa, Uganda, and Zimbabwe. The maximum follow-up period was 2.6 years., Results: One thousand two hundred sixty-one respondents completed PREMIS at their month 3 visit (M3); 2085 at their month 12 visit (M12); and 1010 at both visits. Most participants expressed high expectations of personal benefit (EPB) and that at least one of the rings used in the trial would reduce the risk of getting HIV (expectation of maximum aggregate benefit or EMAB). There was a moderate positive correlation between EPB and EMAB at M3 (r = .43, 95% CI: .37, .47) and M12 (r = .44, 95% CI: .40, .48). However, there was variability among sites in the strength of the relationship. There was no relationship between either expectation variable and condom use, adherence, or HIV infection., Conclusions: A majority of trial participants expressed some belief that their risk of HIV infection would be reduced by using a vaginal ring, which may signal PM. However, such beliefs were not associated with adherence, condom use, or subsequent HIV infection, and there was variability across sites. Further work is needed to understand these findings.

Background Emergent informed consent for clinical trials in acute myocardial infarction (AMI) and stroke is challenging. The role and value of consent are controversial, and insufficient data exist regarding patients' and surrogates' experiences. Methods and Results We conducted structured interviews with patients (or surrogates) enrolled in AMI or acute stroke trials at 6 sites between 2011 and 2016. Primary domains included trial recall, consent experiences, and preferences regarding involvement. Descriptive and test statistics were used to characterize responses and explore relationships between key domains and characteristics. Multivariable logistic regression was used to examine associations between key covariates and consent preferences. There were 176 (84 stroke, 92 AMI) completed interviews. Most stroke respondents (82%) were surrogates; all AMI respondents were patients. Average time from trial enrollment to interview was 1.9 years (stroke) and 2.8 years (AMI); 89% of stroke and 62% of AMI respondents remembered being in the trial, and among these respondents, 80% (stroke) and 44% (AMI) remembered reading some of the consent form. Over 90% reported not feeling pressure to enroll, being treated in a caring way, and being treated with dignity. A minority (16% stroke and 26% AMI) reported they would have preferred not to be asked for consent. Just over half (61% stroke and 53% AMI) recalled a postenrollment conversation about the study. Conclusions Most respondents felt they were treated respectfully and were glad they had been asked for consent. Trial recall was relatively low, and many respondents recalled little postenrollment discussion. Further development of context-sensitive approaches to consent is important.

Purpose: Women with lower urinary tract symptoms are often diagnosed based on a predefined symptom complex or a predominant symptom. There are many limitations to this paradigm as often patients present with multiple urinary symptoms which do not perfectly fit the preestablished diagnoses. We used cluster analysis to identify novel, symptom based subtypes of women with lower urinary tract symptoms., Materials and Methods: We analyzed baseline urinary symptom questionnaire data obtained from 545 care seeking female participants enrolled in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) Observational Cohort Study. Symptoms were measured with the LUTS (lower urinary tract symptoms) Tool and the AUA SI (American Urological Association Symptom Index), and analyzed using a probability based consensus clustering algorithm., Results: Four clusters were identified. The 138 women in cluster F1 did not report incontinence but experienced post-void dribbling, frequency and voiding symptoms. The 80 women in cluster F2 reported urgency incontinence as well as urgency and frequency but minimal voiding symptoms or stress incontinence. Cluster F3 included 244 women who reported all types of incontinence, urgency, frequency and mild voiding symptoms. The 83 women in cluster F4 reported all lower urinary tract symptoms at uniformly high levels. All but 2 of 44 LUTS Tool and 8 AUA SI questions significantly differed between at least 2 clusters (p <0.05). All clusters contained at least 1 member from each conventional group, including continence, and stress, urgency, mixed and other incontinence., Conclusions: Women seeking care for lower urinary tract symptoms cluster into 4 distinct symptom groups which differ from conventional clinical diagnostic groups. Further validation is needed to determine whether management improves using this new classification., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

The original version of the article unfortunately contained an error in Results section of Abstract.