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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 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.

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.

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.

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.

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. Supplementary Information The online version contains supplementary material available at 10.1007/s11606-021-07087-8.

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.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.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.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.

Background: Ureteral stents are commonly employed after ureteroscopy to treat urinary stone disease, but the devices impose a substantial burden of stent-associated symptoms (SAS), including pain and urinary side effects. The NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) Urinary Stone Disease Research Network sought to develop greater understanding of SAS causes and severity among individuals treated ureteroscopically for ureteral or renal stones. Materials and Methods: We designed a prospective, observational cohort study comprising adolescents and adults undergoing ureteroscopic intervention for ureteral or renal stones. Participants will undergo detailed symptom assessment using validated questionnaires, a psychosocial assessment, and detailed collection of clinical and operative data. Quantitative sensory testing will be utilized to assess pain sensitization. In addition, a small cohort (∼40 individuals) will participate in semi-structured interviews to develop more granular information regarding their stent symptoms and experience. Biospecimens (blood and urine) will be collected for future research. Results: The Study to Enhance Understanding of sTent-associated Symptoms (STENTS) enrolled its first participant in March 2019 and completed nested qualitative cohort follow-up in August 2019. After a planned pause, enrollment for the main study cohort resumed in September 2019 and is expected to be completed in 2021. Conclusion: STENTS is expected to provide important insights into the mechanisms and risk factors for severe ureteral SAS after ureteroscopy. These insights will generate future investigations to mitigate the burden of SAS among individuals with urinary stone disease.

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.

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.

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.

The implementation of pragmatic clinical trials (PCTs) can be accompanied by unique regulatory challenges. In this paper, we describe the experience and management of regulatory noncompliance during a 25-site acute care PCT. During the trial, the study team conducted a comprehensive audit of all enrollment forms (informed consent and Health Insurance Portability and Accountability Act authorization forms) and related study documentation. A review of 997 participants' enrollment forms identified 138 (13.8%) that required reporting to the institutional review board due to noncompliance. To prevent subsequent noncompliance, the study team developed and introduced a revised participant tracking system, reviewed all enrollment documentation, and retrained sites regarding study procedures. Based on these experiences, we developed a set of recommendations for future PCTs to ensure both operational success and regulatory compliance.

Background Pragmatic clinical trials (PCTs) are increasingly being conducted to efficiently generate evidence to inform healthcare decision-making. Despite their growing acceptance, PCTs may involve a variety of ethical issues, including the management of pragmatic clinical trial-collateral findings (PCT-CFs), that is, information that emerges in PCTs that is unrelated to the primary research questions but may have implications for patients, clinicians, and health systems. Objective We sought to understand patients' views about PCT-CF disclosure, including how, by whom, and the nature and extent of information provided. Design Prospective, qualitative focus group study. Participants Focus groups were conducted in Baltimore, MD; Houston, TX; and Seattle, WA (overall N = 66), during July and August 2019. Approach All groups discussed a hypothetical scenario involving the detection of a PCT-CF of contraindicated medications. Participants were asked about their reactions to the PCT-CF and issues related to its disclosure. Key results Reactions to learning about the PCT-CF were mixed, ranging from fear of a significant health problem, anger that the contraindicated medications had gone unnoticed and/or for being included in research without their permission, to gratitude for the information. Preferences for how such disclosures are made varied but were driven by several consistent desires, namely minimizing patient harm and anxiety and demonstrating trust and respect. Many wanted their treating clinician to be informed of the PCT-CF so that they would be prepared to answer patients' questions and to discuss treatment options. Conclusions The detection of PCT-CFs is likely to increase with further expansion of PCTs. As such, clinicians will undoubtedly become involved in the management of PCT-CFs. Our data illustrate some of the challenges clinicians may face when their patients are informed of a PCT-CF and the need to develop guidance for disclosing PCT-CFs in ways that align with patients' preferences and values.

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.

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

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.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.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.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.

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.

Pragmatic clinical trials are increasingly used to generate knowledge about real-world clinical interventions. However, they involve some distinctive ethical and regulatory challenges. In this article, we examine a set of issues related to incentives and other payments to patients in pragmatic clinical trials. Although many of the ethical concerns related to incentives and payments in explanatory trials pertain to pragmatic clinical trials, the pragmatic features may introduce additional challenges. These include those related to the risk of incentives and payments undermining the scientific validity and social value of pragmatic clinical trials, the sources of data used in pragmatic clinical trials, and when the pragmatic clinical trials are conducted under waivers of consent. Based on our examination of these matters, we offer some preliminary recommendations regarding incentives and payments in pragmatic clinical trials, recognizing that additional data and experiences are needed to refine them.

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.

Context Pragmatic clinical trials (PCTs), which are becoming widespread since they are relatively inexpensive and offer important benefits for healthcare decision‐making, can also present practical, ethical, and legal challenges. One such challenge involves managing “pragmatic clinical trial collateral findings” (PCT‐CFs), or information emerging in a PCT that is unrelated to the primary research question(s), yet may have implications for individual patients, clinicians, or health care systems from whom or within which data were collected. The expansion of PCTs makes it likely healthcare systems will increasingly encounter PCT‐CFs, yet little guidance exists regarding their appropriate management. Methods We conducted semi‐structured interviews with key stakeholders experienced in the conduct or oversight of PCTs and those in health system leadership. Interviews explored respondents' experience with PCTs and PCT‐CFs, and actual or hypothetical reactions to PCT‐CF management. We used standard methods of qualitative analysis to identify key themes. Findings Forty‐one stakeholders participated. Four key themes emerged. First, discussions of PCT‐CFs are complicated by layers of ambiguity related to both the nature of PCTs themselves, and unanticipated results that emanate from them. Second, management of PCT‐CFs is context‐specific, and not amenable to a “one‐size‐fits‐all” approach. Third, there was a wide diversity of attitudes regarding the scope of researcher responsibilities in PCTs. Fourth, PCT‐CFs had generally not been previously considered by respondents, but there was widespread belief in the importance of prospective planning to anticipate such issues in future PCTs. Conclusions PCT‐CFs are likely to increase, yet those charged with PCT‐CF decision‐making and their disclosure are unlikely to have experience with these issues. Further deliberation about the ethical obligations and implementation processes regarding PCT‐CFs is needed. To enhance the likelihood of developing sound policies and practices, such deliberations should include the input and perspectives of key stakeholders in PCTs, including professionals, policy makers, and patients.

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.

ImportanceCommunication during conversations about death is critical; however, little is known about the language clinicians and families use to discuss death.ObjectiveTo 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 ParticipantsThis 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 MeasuresThe main outcome was the language used to reference death during family meetings between parents and clinicians. Conventional content analysis was used to analyze data.ResultsA 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 RelevanceIn 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.

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.

I was delighted to read Dickert et al.’s (2020) summary of the outstanding work conducted as part of the Patient-Centered Approaches to Research Enrollment Decisions in Acute Cardiovascular Disease...

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.

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.

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.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.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.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.

OBJECTIVES: 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 FS-ICU score ≥ 75, high decisional regret/conflict as DRS/DCS score > 25, and within-couple disagreement as a difference between scores of at least 25 points. RESULTS: We enrolled 61 parents of 40 infants (n = 40 mothers, n = 21 fathers); 35mothers and 15 fathers completed surveys. Most mothers reported high satisfaction with decision-making (n = 27/35, 77%) and low decision regret (n = 28/35, 80%); 40% reported high decisional conflict (n = 14/35). Mothers and fathers reported higher decisional conflict in the domains of uncertainty and values clarity as compared with the domain of effective decision-making (Bonferroni-corrected p-values < 0.05). There were no differences in decision outcomes between paired mothers and fathers. However, within any given couple, there were numerous instances of disagreement (n = 7/15 for decision regret and n = 5/15 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.

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 8...

Background There are multiple treatment options for men with localized prostate cancer that provide similar curative efficacy but differ in their impact on sexual functioning. Aim To evaluate the psychometric properties of the Patient-Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction (SexFS) measures, including items from versions 1 and 2 of the short forms. Methods A population-based cohort of men across North Carolina completed surveys via phone interviews at baseline (prior to treatment) and at 3, 12, and 24 months after cancer treatment initiation. Surveys included the PROMIS SexFS domains of interest in sexual activity, erectile function, orgasm, and satisfaction and the Prostate Cancer Symptom Indices. Analyses included descriptive statistics, assessment of structural validity using confirmatory factor analysis and item response theory, tests for differential item functioning, assessment of convergent validity using correlations, and evaluation of responsiveness of the PROMIS SexFS measures over time. We hypothesized that men undergoing surgery (prostatectomy) would report the poorest sexual function at the 3-month survey. Results Sample size varied by assessment point and ranged from 332‒939 men, consisting of 30% non-white men, and 30% of the sample had a high school degree or less. The items within the PROMIS orgasm domain did not form a unidimensional scale. PROMIS measures of interest in sexual activity, erectile function, and satisfaction were unidimensional and highly correlated with related Prostate Cancer Symptom Indices measures (eg, erectile function, r = 0.84‒0.95). Erectile function in the surgery group declined more at 3 months compared to the no-surgery group (2 points); this difference narrowed at 12 and 24 months after surgery, as the surgery group recovered over time. Results were similar for PROMIS Interest in Sexual Activity and PROMIS Satisfaction scales. Clinical Implications The PROMIS SexFS measures may be used to identify effective interventions to treat sexual dysfunction and monitor sexual functioning in men with prostate cancer over time. Strength & Limitations This study was limited to men living in North Carolina who could self-report their health-related quality of life in English. However, this study was able to include more men from vulnerable populations by allowing them to self-report over the phone. Conclusion This study provided strong support for use of the PROMIS SexFS (version 2) measures in men with localized prostate cancer to assess sexual interest, erectile function, and satisfaction over time.

Objectives There has been limited success in achieving integration of patient-reported outcomes (PROs) in clinical trials. We describe how stakeholders envision a solution to this challenge. Methods Stakeholders from academia, industry, non-profits, insurers, clinicians, and the Food and Drug Administration convened at a Think Tank meeting funded by the Duke Clinical Research Institute to discuss the challenges of incorporating PROs into clinical trials and how to address those challenges. Using examples from cardiovascular trials, this article describes a potential path forward with a focus on applications in the United States. Results Think Tank members identified one key challenge: a common understanding of the level of evidence that is necessary to support patient-reported outcome measures (PROMs) in trials. Think Tank participants discussed the possibility of creating general evidentiary standards depending upon contextual factors, but such guidelines could not be feasibly developed because many contextual factors are at play. The attendees posited that a more informative approach to PROM evidentiary standards would be to develop validity arguments akin to courtroom briefs, which would emphasize a compelling rationale (interpretation/use argument) to support a PROM within a specific context. Participants envisioned a future in which validity arguments would be publicly available via a repository, which would be indexed by contextual factors, clinical populations, and types of claims. Conclusions A publicly available repository would help stakeholders better understand what a community believes constitutes compelling support for a specific PROM in a trial. Our proposed strategy is expected to facilitate the incorporation of PROMs into cardiovascular clinical trials and trials in general.

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.To evaluate molecular recurrence (MRec) and patient-reported outcomes (PROs) after TKI discontinuation for US patients with CML.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.Discontinuation of TKIs.Molecular recurrence, defined as loss of major molecular response (BCR-ABL1 International Scale ratio0.1%) 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).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.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.ClinicalTrials.gov Identifier: NCT02269267.