Administering selected subscales of patient-reported outcome questionnaires to reduce patient burden and increase relevance: a position statement on a modular approach.

Patient-reported outcome (PRO) questionnaires considered in this paper contain multiple subscales, although not all subscales are equally relevant for administration in all target patient populations. A group of measurement experts, developers, license holders, and other scientific-, regulatory-, payer-, and patient-focused stakeholders participated in a panel to discuss the benefits and challenges of a modular approach, defined here as administering a subset of subscales out of a multi-scaled PRO measure. This paper supports the position that it is acceptable, and sometimes preferable, to take a modular approach when administering PRO questionnaires, provided that certain conditions have been met and a rigorous selection process performed. Based on the experiences and perspectives of all stakeholders, using a modular approach can reduce patient burden and increase the relevancy of the items administered, and thereby improve measurement precision and eliminate wasted data without sacrificing the scientific validity and utility of the instrument. The panelists agreed that implementing a modular approach is not expected to have a meaningful impact on item responses, subscale scores, variability, reliability, validity, and effect size estimates; however, collecting additional evidence for the impact of context may be desirable. It is also important to recognize that adequate rationale and evidence (e.g., of fit-for-purpose status and relevance to patients) and a robust consensus process that includes patient perspectives are required to inform selection of subscales, as in any other measurement circumstance, is expected. We believe that the considerations discussed within (content validity, administration context, and psychometric factors) are relevant across multiple therapeutic areas.

A Review of Meaningful Change Thresholds for EORTC QLQ-C30 and FACT-G Within Oncology.

OBJECTIVES: This literature review provides an overview of meaningful change thresholds for the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) and the Functional Assessment of Cancer Therapy - General (FACT-G) used across hematological cancers and solid tumors (melanoma, lung, bladder, and prostate). METHODS: Embase, MEDLINE, and PubMed were searched to identify relevant oncology publications from 2016 to 2021. Label claims from the US Food and Drug Administration and the European Medicines Agency for 7 recently approved drugs (pembrolizumab, atezolizumab, glasdegib, gilteritinib, tisagenlecleucel, axicabtagene ciloleucel, and daratumumab plus hyaluronidase-fihj) were reviewed. RESULTS: Publications providing guidance on meaningful change thresholds for the QLQ-C30 displayed a growing trend away from broad "legacy" thresholds of 10 points for all QLQ-C30 scales), toward deriving "contemporary" thresholds (eg, subscale specific, population specific). Contemporary publications generally provide guidance on selecting thresholds for specific scales that account for improved or worsening thresholds (eg, QLQ-C30 subscales). This trend was not clear for FACT-G, with less new guidance available. Most clinical trials used in regulatory label submissions have used thresholds of 10 points for the QLQ-C30 subscales and 3 to 7 points for the FACT-G total score. Despite the availability of more recent guidelines, contemporary meaningful change thresholds seem slow to emerge in the published literature and regulatory labels. CONCLUSIONS: Trialists should consider using contemporary thresholds, rather than legacy thresholds, for QLQ-C30 endpoints. Thresholds derived for a similar patient-population should be used where available. Further work is required to provide these across a broader range of cancer sites.

Lisocabtagene maraleucel for second-line relapsed or refractory large B-cell lymphoma: patient-reported outcomes from the PILOT study.

In the single-arm, open-label, multicenter, phase II PILOT study, second-line treatment with the chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (liso-cel) in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) for whom hematopoietic stem cell transplantation (HSCT) was not intended resulted in high response rates, durable responses, and a safety profile consistent with previous reports. Here, we analyzed changes in health-related quality of life (HRQOL) in patients who received liso-cel in PILOT. Patients received liso-cel, an autologous, CD19-directed, 4-1BB CAR T-cell product administered at equal target doses of CD8+ and CD4+ CAR+ T cells, for a total target dose of 100×106 CAR+ T cells. HRQOL, a secondary endpoint of PILOT, was assessed as prespecified using three patient-reported outcome instruments (EORTC QLQ-C30; FACT-LymS; EQ-5D-5L). Evaluable datasets for the EORTC QLQ-C30, FACT-LymS, and EQ-5D-5L health utility index, and visual analog scale (EQ-VAS) included 56 (92%), 49 (80%), 55 (90%), and 54 (89%) patients, respectively. Clinically meaningful improvement was achieved across most post-treatment visits for EORTC QLQ-C30 fatigue and FACT-LymS. Overall mean changes from baseline through day 545 showed significant improvements in EORTC QLQ-C30 fatigue, pain, and appetite loss, FACT-LymS, and EQ VAS. In within-patient analyses, clinically meaningful improvements or maintenance in scores were observed in most patients at days 90, 180, 270, and 365. HRQOL was maintained or improved in patients who received liso-cel as second-line therapy in PILOT. These findings support liso-cel as a preferred second-line treatment in patients with R/R LBCL not intended for HSCT (clinicaltrials gov. Identifier: NCT03483103).

Analysis of patient-reported experiences up to 2 years after receiving idecabtagene vicleucel (ide-cel, bb2121) for relapsed or refractory multiple myeloma: Longitudinal findings from the phase 2 KarMMa trial.

OBJECTIVE: To understand the long-term experience of patients receiving ide-cel chimeric antigen receptor T (CAR T) cell therapy for relapsed or refractory multiple myeloma in the pivotal phase 2 KarMMa trial. METHODS: This qualitative study analyzed semi-structured patient interviews 6-24 months after ide-cel infusion. Thematic analysis with quantitative and longitudinal analyses explored patient perceptions of ide-cel treatment experience, advantages and disadvantages, and long-term health-related quality of life impact. Patient journeys were developed from narrative analysis of perceived treatment benefits with known remission length. RESULTS: Interviews with 45 patients 6-24 months postinfusion were analyzed; all reported ≥ 1 ide-cel treatment advantage, most often related to efficacy (n = 42/45, 93%), few or no side effects (n = 35/45, 78%), and avoidance of other treatments (n = 34/45, 76%). Patients generally reported 6-month improvements in physical health, functioning, emotional well-being, social life, and outlook on the future; these improvements mostly remained "stable" through 18 and 24 months. The most common patient journeys comprised physical, functioning, or emotional benefit with remission < 2 years. CONCLUSIONS: Longitudinal analysis of patient experiences showed sustained benefits and preference for ide-cel up to 24 months after treatment. Trial Registration Number and Date: NCT03361748. December 5, 2017.

Adjuvant Therapy of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Patients With Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915).

PURPOSE: Ipilimumab and nivolumab have each shown treatment benefit for high-risk resected melanoma. The phase III CheckMate 915 trial evaluated adjuvant nivolumab plus ipilimumab versus nivolumab alone in patients with resected stage IIIB-D or IV melanoma. PATIENTS AND METHODS: In this randomized, double-blind, phase III trial, 1,833 patients received nivolumab 240 mg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks (916 patients) or nivolumab 480 mg once every 4 weeks (917 patients) for ≤ 1 year. After random assignment, patients were stratified by tumor programmed death ligand 1 (PD-L1) expression and stage. Dual primary end points were recurrence-free survival (RFS) in randomly assigned patients and in the tumor PD-L1 expression-level < 1% subgroup. RESULTS: At a minimum follow-up of approximately 23.7 months, there was no significant difference between treatment groups for RFS in the all-randomly assigned patient population (hazard ratio, 0.92; 95% CI, 0.77 to 1.09; P = .269) or in patients with PD-L1 expression < 1% (hazard ratio, 0.91; 95% CI, 0.73 to 1.14). In all patients, 24-month RFS rates were 64.6% (combination) and 63.2% (nivolumab). Treatment-related grade 3 or 4 adverse events were reported in 32.6% of patients in the combination group and 12.8% in the nivolumab group. Treatment-related deaths were reported in 0.4% of patients in the combination group and in no nivolumab-treated patients. CONCLUSION: Nivolumab 240 mg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks did not improve RFS versus nivolumab 480 mg once every 4 weeks in patients with stage IIIB-D or stage IV melanoma. Nivolumab showed efficacy consistent with previous adjuvant studies in a population resembling current practice using American Joint Committee on Cancer eighth edition, reaffirming nivolumab as a standard of care for melanoma adjuvant treatment.

Health-related quality of life with lisocabtagene maraleucel vs standard of care in relapsed or refractory LBCL.

Lisocabtagene maraleucel (liso-cel) has shown promising efficacy in clinical trials for patients with relapsed/refractory large B-cell lymphoma (LBCL). We present health-related quality of life (HRQOL) results from the TRANSFORM study, the first comparative analysis of liso-cel vs standard of care (SOC) as second-line therapy in this population. Adults with LBCL refractory or relapsed ≤12 months after first-line therapy and eligible for autologous stem cell transplantation were randomized 1:1 to the liso-cel or SOC arms (3 cycles of immunochemotherapy in which responders proceeded to high-dose chemotherapy and autologous stem cell transplantation). HRQOL was assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - 30 items and the Functional Assessment of Cancer Therapy-Lymphoma subscale. Patients with baseline and ≥1 postbaseline assessment were analyzed (liso-cel, n = 47; SOC, n = 43). The proportion of patients with meaningful improvement in global health status/quality of life (QOL) was higher, whereas deterioration was lower in the liso-cel arm vs SOC arm from day 126 to month 6. Mean change scores showed meaningful worsening in global health status/QOL at month 6, fatigue at day 29 and month 6, and pain at month 6 with SOC; mean scores for other domains were maintained or improved in both arms. Time to confirmed deterioration favored the liso-cel arm vs SOC arm in global health status/QOL (median: not reached vs 19.0 weeks, respectively; hazard ratio, 0.47; 95% confidence interval, 0.24-0.94). HRQOL was either improved or maintained from baseline in patients with relapsed/refractory LBCL in the liso-cel arm vs SOC arm as second-line treatment. This study is registered at clinicaltrials.gov as #NCT0357531.

Patient experience before and after treatment with idecabtagene vicleucel (ide-cel, bb2121): qualitative analysis of patient interviews in the KarMMa trial.

OBJECTIVE: To understand the experience of patients with relapsed and refractory multiple myeloma (RRMM) receiving idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, in the pivotal, phase 2 KarMMa trial. METHODS: Optional semi-structured interviews before leukapheresis (pre-treatment) captured expectations and after ide-cel infusion (1, 2, and 3 months post-treatment), assessed treatment experience, ide-cel advantages/disadvantages, and health and well-being. In a mixed-method analysis, treatment experiences were categorized by clinical response status, health and well-being, and self-reported recovery after infusion. RESULTS: Pre-treatment interviews indicated unmet treatment needs. In post-treatment interviews, most patients reported the positives of ide-cel outweighed negatives (69%, n = 27/39). Most common advantages of ide-cel were efficacy (18-64%), favorable side-effect profile (46-68%), and recovery time (13-18%); most common disadvantages were related to side effects (13-20%). When analyzed by clinical response, patients most often had stringent complete or very good partial response and improved health and well-being with mild or severe recovery from the infusion (27/58, 47%). Most patients with minimal clinical response reported mild infusion recovery (5/6, 83%). CONCLUSIONS: Patient interviews before ide-cel treatment showed unmet needs in triple-class exposed RRMM. Post-treatment experiences generally favored ide-cel versus previously received treatments.

Health-related Quality of Life with Adjuvant Nivolumab After Radical Resection for High-risk Muscle-invasive Urothelial Carcinoma: Results from the Phase 3 CheckMate 274 Trial.

BACKGROUND: The programmed death-1 (PD-1) inhibitor nivolumab prolongs disease-free survival in patients with muscle-invasive urothelial carcinoma (MIUC). OBJECTIVE: To evaluate the effects of nivolumab on health-related quality of life (HRQoL) after radical resection in patients with MIUC. DESIGN, SETTING, AND PARTICIPANTS: We used data from 709 patients in CheckMate 274 (NCT02632409; 282 with programmed death ligand 1 [PD-L1] expression ≥1%), an ongoing randomized, double-blind, placebo-controlled phase 3 trial of adjuvant nivolumab. INTERVENTION: Intravenous injection of nivolumab (240 mg) or placebo every 2 wk for ≤1 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EQ-5D-3L. Linear mixed-effect models for repeated measures were used to compare nivolumab and placebo on changes in HRQoL. Time to confirmed deterioration (TTCD) of HRQoL was analyzed by Cox proportional hazards regression. RESULTS AND LIMITATIONS: In the full HRQoL evaluable population, no clinically meaningful deterioration of HRQoL was observed in either treatment arm. Moreover, nivolumab was noninferior to placebo on changes from baseline for all main outcomes. The median TTCD for fatigue was 41.0 wk for nivolumab and 44.3 wk for placebo (hazard ratio [HR]: 1.11, 95% confidence interval [CI], 0.89-1.39). For the visual analog scale, the median TTCD was not reached for nivolumab and it was 57.6 wk for placebo (HR: 0.78, 95% CI, 0.61-1.00). The median TTCD for the other main outcomes was not reached in either treatment arm. The findings were similar for patients with PD-L1 expression ≥1%. CONCLUSIONS: These results demonstrate that nivolumab did not compromise the HRQoL of patients with MIUC in CheckMate 274. PATIENT SUMMARY: Nivolumab is being researched as a new treatment for patients with bladder cancer (urothelial carcinoma). We found that nivolumab maintained quality of life while increasing the time until cancer returns in patients whose bladder cancer had spread or grown and who had unsuccessfully tried platinum-containing chemotherapy.

Novel linguistic evaluation of prefrontal synthesis (LEPS) test measures prefrontal synthesis acquisition in neurotypical children and predicts high-functioning versus low-functioning class assignment in individuals with autism.

In order to grasp the difference between "the cat on the mat" and "the mat on the cat," understanding the words and the grammar is not enough. Rather it is essential to visualize the cat and the mat together to appreciate their relations. This type of imagination, which involves juxtaposition of mental objects is conducted by the prefrontal cortex and is therefore called Prefrontal Synthesis (PFS). PFS acquisition has a strong experience-dependent critical period putting children with language delay in danger of never acquiring PFS and, consequently, not mastering complex language comprehension. In typical children, the timeline of PFS acquisition correlates with vocabulary expansion. Conversely, atypically developing children may learn many words but never acquire PFS. In these individuals, intelligence tests based on vocabulary assessment may miss the profound deficit in PFS. Accordingly, we developed a test specific for PFS - Linguistic Evaluation of Prefrontal Synthesis or LEPS - and administered it to 50 neurotypical children, age 4.1 ± 1.3 years and to 23 individuals with impairments, age 16.4 ± 3.0 years. All neurotypical children older than 4 years received the LEPS score 7/10 or greater indicating good PFS ability. Among individuals with impairments only 39% received the LEPS score 7/10 or greater. LEPS was 90% correct in predicting high-functioning vs. low-functioning class assignment in individuals with impairments.

Health-related quality of life with idecabtagene vicleucel in relapsed and refractory multiple myeloma.

Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, showed deep, durable responses in patients with triple-class exposed, relapsed and refractory multiple myeloma (RRMM) in the phase 2 KarMMa (Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma) trial. We assessed health-related quality of life (HRQoL) among KarMMa patients. The European Organization for Research and Treatment of Cancer Quality of Life C30 Questionnaire and its supplementary 20-item multiple myeloma module, as well as the EuroQol 5-dimension 5-level instrument, were administered at screening, baseline (≤72 hours before or same day as lymphodepletion), day of ide-cel treatment, and after ide-cel treatment. Mean changes from baseline that exceeded the predetermined threshold of minimally important difference were deemed clinically meaningful. The proportions of patients experiencing clinically meaningful changes in HRQoL were assessed using within-patient change thresholds. Time to stable improvement (≥2 consecutive visits with clinically meaningful HRQoL improvements) was analyzed by using the Kaplan-Meier method. A total of 126 (98%) of 128 patients treated with ide-cel were included in the HRQoL analysis. Pretreatment baseline RRMM burden was high and meaningfully worse than that in the age- and sex-weighted general population. Statistically significant and clinically meaningful improvements from baseline were observed by month 1 for pain (-8.9) and disease symptoms (-10.2), and by month 2 for fatigue (-7.2), physical functioning (6.1), cognitive functioning (6.7), and global health status/QoL (8.0). Clinically meaningful improvements in fatigue, pain, and physical functioning were most prominent at months 9, 12, and 18, respectively, and were sustained through 15 to 18 months after ide-cel treatment. For triple-class exposed patients with RRMM with a poor prognosis and few treatment options, a single ide-cel infusion provides early, sustained, statistically significant, and clinically meaningful improvements in HRQoL. This study was registered at Clinicaltrials.gov as #NCT03361748.

Evaluation of Minimal Important Difference and Responder Definition in the EORTC QLQ-PAN26 Module for Assessing Health-Related Quality of Life in Patients with Surgically Resected Pancreatic Adenocarcinoma.

BACKGROUND: Although the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-PAN26 is widely used to assess health-related quality of life (HRQoL), its group-level minimal important difference (MID) and individual-level responder definition (RD) are not established; we calculated MID and RD using HRQoL data from the APACT trial in patients with surgically resected pancreatic cancer who received adjuvant chemotherapy. METHODS: HRQoL was assessed using EORTC QLQ-C30 and QLQ-PAN26 at baseline, during treatment, at end of treatment, and during follow-up. Distribution-based MIDs were estimated using 0.5 × baseline standard deviation (SD) and reliability-based (intraclass correlation) standard error of measurement (SEM). Anchor-based MIDs and RDs (anchor, QLQ-C30 overall health) were estimated using a linear mixed model. RESULTS: Overall, 772 patients completed the baseline assessment. Distribution-based MIDs (0.5 × SD) for QLQ-PAN26 scales ranged from 12 to 13, except hepatic symptoms (≈8), pancreatic pain (≈10), and sexual dysfunction (≈17); those for stand-alone items ranged from 12 to 16. The SEM values were similar. Among scales/items sufficiently correlated (r > 0.30) with the anchor, MIDs ranged from 5 to 9. Within-patient QLQ-PAN26 RD estimates varied by direction (deterioration vs. improvement) and scale/item, but all values were lower than the true possible within-patient change (e.g. 16.7 points for a two-item scale) given a one-category change on the raw scale. CONCLUSIONS: Compared with distribution-based MIDs, anchor-based MIDs were twice as sensitive in detecting group-level changes in QLQ-PAN26 scales/items. For interpreting clinically meaningful change, RDs cannot be less than the true minimum of the scale. The group-level MID may help clinicians/researchers interpret HRQoL changes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01964430; Eudra CT 2013-003398-91.

Measurement of Quality of Life in Patients with Mycosis Fungoides/Sézary Syndrome Cutaneous T-Cell Lymphoma: Development of an Electronic Instrument.

BACKGROUND: Although the quality of life (QoL) plays an important role in treatment decision making and clinical management of mycosis fungoides (MF) or Sézary syndrome (SS) subtypes of cutaneous T-cell lymphomas (MF/SS-CTCLs), an MF- or SS-specific measure of QoL does not exist. OBJECTIVE: The objective of this research was to develop and validate the first QoL instrument for MF/SS-CTCL using a patient-centered approach. METHODS: A conceptual framework for the MF/SS-CTCL QoL was developed through a literature review and interviews with key opinion leaders. Concept elicitation with patients was utilized to refine the conceptual model and generate preliminary items. The items were then revised based on qualitative and quantitative feedback obtained through cognitive debriefing surveys and interviews with patients. Next, participants (N=126) completed the preliminary MF/SS-CTCL QoL and a comparator measure of health-related QoL (Skindex-29) through the PatientsLikeMe Open Research Exchange. The MF/SS-CTCL QoL was completed again 5 days later by 66 participants for the purposes of evaluating test-retest reliability. The MF/SS-CTCL QoL was finalized based on results from an empirical evaluation, which included both classical and modern test theory approaches. Specifically, this included evaluation of (1) the optimal item response theory measurement model; (2) item fit; (3) unidimensionality; (4) rating scale performance; (5) reliability; (6) test information (precision); (7) person-to-item map; (8) convergent and discriminant validity; and (9) presence of bias via differential item function. RESULTS: Results from the comprehensive psychometric evaluation utilizing a Rasch-Grouped Rating Scale model yielded a final 12-item instrument. The rating scale functioned as expected, and the instrument exhibited adequate person reliability (.87), good to excellent test-retest reliability (r=.89, P<.001), high levels of measurement precision, and good person-to-item targeting. The correlation between the MF/SS-CTCL QoL and the Skindex-29 (r=.852, P<.001) was significantly greater than the correlation between the MF/SS-CTCL QoL and syndrome stage (r=.260, P<.001), providing support for convergent and discriminant validity. Items did not show significant bias based on gender, age, or race. Rasch scores were converted to scaled scores with qualitative descriptive categories for ease of interpretation. CONCLUSIONS: Empirical evaluation demonstrated strong evidence of excellent psychometric properties. Utilizing a patient-centered measure development approach ensures that this QoL instrument captures the information that is most meaningful and clinically relevant to patients.

Development of the Mental Synthesis Evaluation Checklist (MSEC): A Parent-Report Tool for Mental Synthesis Ability Assessment in Children with Language Delay.

Mental synthesis is the conscious purposeful process of synthesizing novel mental images from objects stored in memory. Mental synthesis ability is essential for understanding complex syntax, spatial prepositions, and verb tenses. In typical children, the timeline of mental synthesis acquisition is highly correlated with an increasing vocabulary. Children with Autism Spectrum Disorder (ASD), on the other hand, may learn hundreds of words but never acquire mental synthesis. In these individuals, tests assessing vocabulary comprehension may fail to demonstrate the profound deficit in mental synthesis. We developed a parent-reported Mental Synthesis Evaluation Checklist (MSEC) designed to assess mental synthesis acquisition in ASD children. The psychometric quality of MSEC was tested with 3715 parents of ASD children. Internal reliability of the 20-item MSEC was good (Cronbach's alpha >0.9). MSEC exhibited adequate test⁻retest reliability; good construct validity, supported by a positive correlation with the Autism Treatment Evaluation Checklist (ATEC) Communication subscale; and good known group validity reflected by the difference in MSEC scores for children of different ASD severity levels. The MSEC questionnaire is copyright-free and can be used by researchers as a complimentary subscale for the ATEC evaluation. We hope that the addition of MSEC will make the combined assessment more sensitive to small steps in a child's development. As MSEC does not rely on productive language, it may be an especially useful tool for assessing the development of nonverbal and minimally verbal children.

Autism Treatment Evaluation Checklist (ATEC) Norms: A "Growth Chart" for ATEC Score Changes as a Function of Age.

Most early-intervention Autism Spectrum Disorder (ASD) clinical trials are limited by the availability of psychometric technicians who assess each child's abilities before and after therapeutic intervention. If parents could administer regular psychometric evaluations of their children, then the cost of clinical trials will be reduced, enabling longer clinical trials with the larger number of participants. The Autism Treatment Evaluation Checklist (ATEC) was designed nearly two decades ago to provide such a tool, but the norms on the longitudinal changes in ATEC in the "treatment as usual" population were lacking. Here we report the norms of the observational cohort who voluntarily completed ATEC evaluations over the period of four years from 2013 to 2017.

Communicating laboratory test results for rheumatoid factor: what do patients and physicians want?

OBJECTIVE: This study aimed to explore patient and physician perspectives on current laboratory test reporting practices and to elicit ideas for improvement. METHODS: Two independent studies were conducted. The first solicited members of an online physician community for opinions on current laboratory test reporting practices and possible improvements. The second addressed the same topic, but solicited patient feedback, and included an evaluation of a mock laboratory test report for the rheumatoid factor blood test. RESULTS: Both physicians and patients expressed a desire for patient-friendly information on laboratory reports. Physicians expressed a need for education for patients around false-positive and false-negative results within laboratory reports, while patients sought context around the meaning of results, relevance to other tests, and follow-up steps. CONCLUSION: Physicians and patients see value in enhancing laboratory test reports to improve communication. While reports should include the context that patients value, they should also contain cautionary interpretation emphasized by physicians. Patient consultation on improving laboratory reports may help improve such patient-focused communication and promote greater patient understanding of health information, thereby increasing patient participation in their own health care and improving outcomes. PRACTICE IMPLICATIONS: Laboratory reports are typically designed by experts. Including patients in laboratory report design may facilitate communication and improve outcomes through better patient engagement.

Patients' motivations and interest in research: characteristics of volunteers for patient-led projects on PatientsLikeMe.

PLAIN ENGLISH SUMMARY: PLM is an online platform that provides tools for individuals to track their health and connect with other patients and while PLM has invited patients to participate in various research projects throughout the years, an examination into what motivates patients to want to get involved in clinical research has not been done. During our analysis of applications submitted by members of the PLM community, we looked for reasons patients want to participate in research and their overall beliefs about clinical research, in general. In addition, we analyzed obstacles and barriers toward patients' research participation. We observed the following:Patients are typically motivated by their individual needs and are most interested in research specific to their own condition.To get the most from patients' involvement and to enhance patients' contribution towards research goals, researchers should explain the research goal and requirements of each goal in clear and transparent terms, making it easy for patients to understand, thus avoiding any potential miscommunication.Future studies are needed to determine the best methods for involving patients in clinical research. BACKGROUND: Historically, throughout the clinical and medical research arenas, patients have been perceived as passive "subjects" rather than as individuals who may have thoughts regarding research development, research plans, implementation of research studies, and data analysis. However, it is becoming more clear that patients increasingly want to have a more active role in clinical research studies and in the management of their own medical conditions as evidenced by a "no decision about us without us" stance, meaning patients want to make informed decisions about their health while working alongside their healthcare professionals. The central aim of this research study was to determine patients' motivations for being involved in research design and understand their perceptions of current research practices. METHODS: Two independent qualitative studies were conducted. In Study 1, we analyzed applications submitted by self-identified patients from within the PatientsLikeMe (PLM) community, for acceptance onto our advisory panel. The advisory panel was tasked with developing a best practice guide for how to involve patients in research. During the qualitative analysis, we identified major reasons for and topics of interest associated with PLM members' motivation to apply to the advisory panel. In Study 2, we analyzed applications from PLM community members and from patients outside the PLM community for a patient-led patient-reported-outcome (PRO) development project. Similar to Study 1, we identified themes associated with patients' motivations to participate in developing a new PRO. RESULTS: PLM members are interested in being involved in medical research for various reasons, including facilitating provider-patient communication, improving comprehension of medical information, understanding their disease, and bringing a more individualized approach to health care in general. CONCLUSION: Challenges in the process of appropriate involvement of patients in research are discussed. In both studies, the applicants shared their interests in being involved in research. However, in Study 2, many of the patients shared ideas that were not appropriate for the development of a PRO, which indicated limitations in how the invitation and application explained the project to patients. Future studies should contribute to determining the most appropriate method for involving patients in various settings.

Tilting at windmills: a comment on Auer and Griffiths.

In their review of Internet gambling studies, Auer and Griffiths (Soc Sci Comput Rev 20(3):312-320, 2013) question the validity of using bet size as an indicator of gambling intensity. Instead, Auer and Griffiths suggest using "theoretical loss" as a preferable measure of gambling intensity. This comment identifies problems with their argument and suggests a convergent rather than an exclusionary approach to Internet gambling measures and analysis.