Obstacles to Biosimilar Acceptance and Uptake in Oncology: A Review.

Importance: Biosimilar drugs provide cost-effective yet clinically indistinguishable replications of target drugs. During initial development, this class of biologic medicines was expected to revolutionize pharmaceutical markets; however, following US Food and Drug Administration approval of the first biosimilar drug in 2015, the commercialization of biosimilars has been limited. The lack of biosimilar use may be especially salient in oncology, given that biosimilar distribution in this particularly high-cost area of medicine would bring savings on the order of many billions of dollars. Observations: While researchers have focused on salient economic barriers to biosimilar uptake in the US, the present review provides insight regarding noneconomic barriers. This review discusses psychological, attitudinal, and educational factors among both health care professionals and payers in the US that may play a role in slowing biosimilar uptake. More specifically, these factors include a lack of health care professional education, concerns of safety and efficacy, and overly complex product naming systems. Conclusions and Relevance: The pathway to biosimilar use has been obstructed by economic elements as well as attitudinal and psychological factors. For biosimilar drugs to achieve their potential in decreasing treatment costs and thus increasing patient access, it will be essential for both economic and noneconomic factors to be identified and systematically addressed.

A qualitative evaluation of factors influencing Tumor Treating fields (TTFields) therapy decision making among brain tumor patients and physicians.

BACKGROUND: Tumor Treating Fields (TTFields) Therapy is an FDA-approved therapy in the first line and recurrent setting for glioblastoma. Despite Phase 3 evidence showing improved survival with TTFields, it is not uniformly utilized. We aimed to examine patient and clinician views of TTFields and factors shaping utilization of TTFields through a unique research partnership with medical neuro oncology and medical social sciences. METHODS: Adult glioblastoma patients who were offered TTFields at a tertiary care academic hospital were invited to participate in a semi-structured interview about their decision to use or not use TTFields. Clinicians who prescribe TTFields were invited to participate in a semi-structured interview about TTFields. RESULTS: Interviews were completed with 40 patients with a mean age of 53 years; 92.5% were white and 60% were male. Participants who decided against TTFields stated that head shaving, appearing sick, and inconvenience of wearing/carrying the device most influenced their decision. The most influential factors for use of TTFields were the efficacy of the device and their clinician's opinion. Clinicians (N = 9) stated that TTFields was a good option for glioblastoma patients, but some noted that their patients should consider the burdens and benefits of TTFields as it may not be the desired choice for all patients. CONCLUSIONS: This is the first study to examine patient decision making for TTFields. Findings suggest that clinician support and efficacy data are among the key decision-making factors. Properly understanding the path to patients' decision making is crucial in optimizing the use of TTFields and other therapeutic decisions for glioblastoma patients.

Comparing the Safety Action Feedback and Engagement (SAFE) Loop with an established incident reporting system: Study protocol for a pragmatic cluster randomized controlled trial.

Background: Incident reporting is widely used in hospitals to improve patient safety, but current reporting systems do not function optimally. The utility of incident reports is limited because hospital staff may not know what to report, may fear retaliation, and may doubt whether administrators will review reports and respond effectively. Methods: This is a clustered randomized controlled trial of the Safety Action Feedback and Engagement (SAFE) Loop, an intervention designed to transform hospital incident reporting systems into effective tools for improving patient safety. The SAFE Loop has six key attributes: obtaining nurses' input about which safety problems to prioritize on their unit; focusing on learning about selected high-priority events; training nurses to write more informative event reports; prompting nurses to report high-priority events; integrating information about events from multiple sources; and providing feedback to nurses on findings and mitigation plans. The study will focus on medication errors and randomize 20 nursing units at a large academic/community hospital in Los Angeles. Outcomes include: (1) incident reporting practices (rates of high-priority reports, contributing factors described in reports), (2) nurses' attitudes toward incident reporting, and (3) rates of high-priority events. Quantitative analyses will compare changes in outcomes pre- and post-implementation between the intervention and control nursing units, and qualitative analyses will explore nurses' experiences with implementation. Conclusion: If effective, SAFE Loop will have several benefits: increasing nurses' engagement with reporting, producing more informative reports, enabling safety leaders to understand problems, designing system-based solutions more effectively, and lowering rates of high-priority patient safety events.

Integrating PROMIS Measures in a Treat-to-Target Approach to Standardize Patient-Centered Treatment of Rheumatoid Arthritis.

OBJECTIVE: To evaluate the effect of a patient-centered rheumatoid arthritis (RA) treat-to-target (T2T) disease management approach on patient outcomes and patient satisfaction with care. METHODS: In this longitudinal, observational pilot study, rheumatologists implemented a modified T2T approach that integrated Patient Reported Outcomes Measurement Information System (PROMIS) measures for depression, fatigue, pain interference, physical function, and social function into RA care. Study participants selected 1 PROMIS domain to target treatment and completed quarterly follow-up assessments. Participants were classified as improved if their Clinical Disease Activity Index (CDAI) changed by > 5 points. Change in PROMIS t scores was examined for the group with improved CDAI, and then compared to those with unchanged or worsened CDAI. Satisfaction with care was assessed using multiple measures, including the Functional Assessment of Chronic Illness Therapy-Treatment Satisfaction-Patient Satisfaction Scale. RESULTS: The analytical sample (n = 119, median age 57 years, 90.8% female) was split between those with CDAI > 10 (n = 63) and CDAI ≤ 10 (n = 53). At 1 year, there was improvement in CDAI by > 5 points in 66% and 13% of individuals with baseline CDAI > 10 and baseline CDAI ≤ 10, respectively. Across all participants, improvement in CDAI by > 5 points correlated with improvements in the 5 PROMIS domains. Satisfaction with RA treatment also increased. CONCLUSION: The integration of PROMIS measures into the T2T approach for RA care was associated with improvements in disease activity, and improvement in disease activity was associated with improvements in PROMIS measures.

Medical Oncologists' Knowledge and Perspectives on the Use of Biosimilars in the United States.

PURPOSE: Despite increasing availability of biosimilar cancer treatments, little is known about oncologists' knowledge and concerns regarding biosimilar use in the United States. We surveyed medical oncologists to examine their knowledge, attitudes, and experience with biosimilars. METHODS: Oncologists recruited via the ASCO Research Survey Pool completed a 29-question survey in 2020 designed with input from clinical and health care system experts and literature review. RESULTS: Of the 269 respondents, most treated patients with biosimilars (n = 236, 88%) and reported that biosimilars were required at their institution (n = 168, 63%). Approximately half (n = 140, 52%) of oncologists correctly responded that biosimilars were not the same as generic medicines. Commonly reported barriers to use of biosimilars included concerns regarding a perceived lack of relevant research (n = 85, 33% reporting quite a bit/very much), the potential for extrapolation (n = 83, 33%), and efficacy limitations (n = 77, 30%). More oncologists from university hospitals (n = 36, 22%) than from community/private hospitals (n = 28, 38%) or private practices (n = 13, 38%) were concerned about biosimilar efficacy. A high proportion of oncologists reported that information on safety (n = 259, 99%) and efficacy (n = 255, 99%) is important when considering whether to use biosimilars. Less than half reported that their institution provided education about biosimilars (n = 108, 40%). CONCLUSION: In this sample of medical oncologists, knowledge about basic features of biosimilars was limited and access to information about biosimilars was insufficient. The present study determined that educational programs on biosimilars for oncologists are needed and identified priorities for such efforts.

Qualitative development of the PROMIS Profile v1.0-Familial Chylomicronemia Syndrome (FCS) 28.

PURPOSE: Familial chylomicronemia syndrome (FCS) is a rare genetic disorder characterized by high triglyceride levels, significant disease burden, and negative impacts on health-related quality of life. This project aimed to create a PROMIS-based patient-reported outcome measure that represents valid and important concerns for patients with FCS. METHODS: We reviewed the literature and data from a previous qualitative study of FCS to identify key FCS symptoms and impacts, which were mapped to PROMIS domains to create a pool of eligible items. Candidate items were reduced per expert feedback and patients with FCS completed cognitive interviews to confirm content validity and measure content. RESULTS: Literature and qualitative data review identified ten key symptoms and 12 key impacts of FCS, including abdominal pain, fatigue, difficulty thinking, and worry about pancreatitis attacks. We identified 96 items primarily from PROMIS, supplemented with items from the Quality of Life in Neurological Disorders™ (Neuro-QoL™) and the Functional Assessment of Chronic Illness Therapy (FACIT) measurement systems. This pool was reduced to 32 candidate items, which were assessed via cognitive interviews with eight participants with FCS. Cognitive interview results and additional expert feedback led to the removal of four items and finalization of the PROMIS Profile v1.0-familial chylomicronemia syndrome (FCS) 28. CONCLUSIONS: The PROMIS Profile v1.0-familial chylomicronemia syndrome (FCS) 28 provides strong content validity for assessing quality of life among patients with FCS. The benefits of PROMIS, including norm-referenced mean values for each measure, will facilitate comparison of patients with FCS to other clinical populations.

How do patients interpret and respond to a single-item global indicator of cancer treatment tolerability?

BACKGROUND: There is increasing interest in patient-reported measures of cancer treatment tolerability. A global measure of bother, the FACT GP5 item ("I am bothered by side effects of treatment") is potentially useful for regulatory, research, and clinical use. To understand this item's appropriateness for capturing treatment tolerability, we conducted cognitive interviews on this item with 3 samples of cancer patients. METHODS: Patients with ovarian cancer (Study 1: N = 21; on treatment), lymphoma (Study 2: N = 14; on treatment), and colorectal or lung cancer (Study 3: N = 16; treatment naïve) were interviewed about GP5's understandability and relevance to their treatment side effects. What patients think about when answering GP5 was also assessed. In all studies, the interview included both structured and open-ended questions. Qualitative data were coded to extract themes and responses to structured questions were tallied. RESULTS: Most patients on treatment (Studies 1 and 2) reported that the GP5 item wording is appropriate (88%) and its meaning is clear (97%). They were very confident or confident in their response (97%) and stated that GP5 was relevant to their cancer experience (97%). When answering GP5, patients considered their treatment and specific side effects. A large proportion (40%) of the treatment-naïve (Study 3) patients reported that GP5 was not relevant to their cancer treatment, and the largest proportion responded to GP5 thinking of negative side effect expectancies. CONCLUSION: This study provides assurance that GP5 is a useful indicator of treatment tolerability, and is meaningful to people with cancer, especially once they have started treatment.

Navigating medication-taking after kidney transplant.

BACKGROUND: Mixed methods are valuable in understanding multifaceted health behaviors like medication adherence. Kidney transplant recipients (KTRs) have complex medication regimens and are more vulnerable to nonadherence relative to other transplant recipients. Yet mixed methods have not been widely applied to examine adherence among KTRs, especially in relation to prescribed medications beyond immunosuppressants. OBJECTIVES: As part of a sequential approach, we used in-depth interviews to better understand findings from a previous quantitative study and to describe additional factors that influence prescription medication-taking among adult KTRs. METHODS: Semi-structured interviews were conducted with a purposive sample of 14 adult KTRs recruited from a transplant center in Chicago, IL. Deductive and inductive content analysis was used to code transcripts and identify key themes. RESULTS: Across the sample, we identified insurance challenges, disruptions in routine, and poor mental well-being as barriers to adherence at the patient level. For Black and Hispanic KTRs, poor communication between providers and disjointed care transitions posed additional barriers at the health system level. Compared with White KTRs, Black and Hispanic KTRs experienced greater medication burden due to comorbidities, while medication and digital literacy challenges were unique to Hispanic KTRs. CONCLUSION: KTRs are often motivated to take medications as prescribed, but sometimes lack the capacity or support to do so. Eliciting KTR perspectives is necessary in addressing knowledge and resource gaps at the patient and health system levels to improve adherence. In addition, recognizing the relative burden of taking comorbidity medications compared with immunosuppressants may important, particularly for Black and Hispanic KTRs.

Optimizing a Behavioral Sleep Intervention for Gynecologic Cancer Survivors: Study Design and Protocol.

Sleep difficulties, particularly symptoms of insomnia and circadian disruption, are among the primary complaints of gynecologic cancer survivors before, during, and after treatment. Moreover, difficulty sleeping has been linked to poorer health-related quality of life and elevated symptom burden in this population. Although leading behavioral sleep interventions have demonstrated efficacy among cancer survivors, up to 50% of survivors are non-adherent to these treatments, likely because these interventions require labor-intensive behavior and lifestyle changes. Therefore, there is a need for more effective and acceptable approaches to diminish sleep disturbance among cancer survivors. This manuscript describes the methodology of a two-part study guided by the Multiphase Optimization Strategy (MOST) framework to identify a streamlined behavioral sleep intervention for gynecologic cancer survivors. Three candidate intervention components previously shown to decrease sleep disturbance will be evaluated, including sleep restriction, stimulus control, and systematic bright light exposure. Participants will be adult women with a history of non-metastatic gynecologic cancer who have completed primary treatment and who report current poor sleep quality. Fifteen participants will be recruited for Part 1 of the study, which will utilize qualitative methods to identify barriers to and facilitators of intervention adherence. Results will inform changes to the delivery of the candidate intervention components to promote adherence in Part 2, where 80 participants will be recruited and randomized to one of eight conditions reflecting every possible combination of the three candidate intervention components in a full factorial design. Participants will complete assessments at baseline, post-intervention, and 3-months post-intervention. Part 2 results will identify the combination of candidate intervention components that yields the most efficacious yet efficient 6-week intervention for diminishing sleep disturbance. This is the first known study to apply the MOST framework to optimize a behavioral sleep intervention and will yield a resource-efficient treatment to diminish sleep disturbance, improve health-related quality of life, and decrease symptom burden among gynecologic cancer survivors. ClinicalTrials.gov Identifier: NCT05044975.

Interprofessional Healthcare Students' Attitudes, Skills, and Knowledge After Comprehensive Pain Assessment Training in Verbal and Nonverbal Patients.

A comprehensive pain assessment is the first step in safe, effective pain management. Few studies have explored variations of strategies and measures for multidimensional pain assessment education in both verbal and nonverbal patients. In this retrospective cohort study, interprofessional health care students enrolled in a palliative care curriculum completed a pain assessment training, which taught the PQRSTA ("palliating factors, precipitating factors, previous treatments, quality, region, radiation, severity, temporal factors and associated symptoms") mnemonic as a strategy for assessing pain in verbal patients and the Pain Assessment in Advance Dementia and Checklist of Nonverbal Pain Indicators measures for nonverbal patients. The purpose of this study was to compare the change in attitudes, self-perceived skills, and knowledge regarding pain assessment before and after the training. Attitudes and self-perceived skills were assessed in the pretraining and posttraining survey, which was analyzed using χ2 test or Fisher exact test. Students' knowledge responses were analyzed using Wilcoxon signed rank test to assess accuracy of responses compared with the expert defined score. One hundred eighty-two students were included. Results showed a statistically significant improvement in attitudes related to applicability of pain measures and self-perceived skills. Overall, data did not support an increase in knowledge using the PQRSTA mnemonic, or Pain Assessment in Advance Dementia and Checklist of Nonverbal Pain Indicators measures. Future pain trainings should consider training on only 1 nonverbal pain measure, incorporating bedside assessments, and integrating real-time feedback.

Development of the Functional Assessment of Cancer Therapy-Carcinoid Syndrome Symptom Index.

OBJECTIVE: To develop a symptom-focused index to evaluate representative symptoms, treatment side effects, and emotional and functional well-being of patients with carcinoid syndrome (CS). METHODS: The development of the Functional Assessment of Cancer Therapy-Carcinoid Syndrome Symptom Index (FACT-CSI) followed US Food and Drug Administration guidelines for the development of patient-reported outcome (PRO) measures and involved the following: (a) literature review; (b) interviews with 14 CS patients; (c) interviews with 9 clinicians; and (d) instrument development involving input from a range of PRO measure development and CS experts. The resulting draft instrument underwent cognitive interviews with 7 CS patients. RESULTS: Forty-six CS sources were reviewed. Analysis of patient interviews produced 23 patient-reported symptoms. The most frequently endorsed physical symptoms were flushing, diarrhea, abdominal pain, fatigue, and food sensitivity/triggers. Seven priority CS emotional and functional themes were also identified by patients. Expert interviews revealed 12 unique priority symptoms - the most common being diarrhea, flushing, wheezing, edema, abdominal pain/cramping, fatigue, and 8 emotional and functional concerns. Through an iterative process of team and clinical collaborator meetings, data review, item reduction and measure revision, 24 items were selected for the draft symptom index representing symptoms, emotional concerns, global assessment of treatment side effects, and functional well-being. Cognitive interview results demonstrated strong content validity, including positive endorsement of item clarity (>86% across items), symptom relevance (>70% for most items), and overall measure content (86%). CONCLUSIONS: The FACT-CSI is a content-relevant, symptom-focused index reflecting the highest priority and clinically relevant symptoms and concerns of people with CS.

Patient preferences and quality of life implications of ravulizumab (every 8 weeks) and eculizumab (every 2 weeks) for the treatment of paroxysmal nocturnal hemoglobinuria.

BACKGROUND: Eculizumab has transformed management of paroxysmal nocturnal hemoglobinuria (PNH) since its approval. However, its biweekly dosing regimen remains a high treatment burden. Ravulizumab administered every 8 weeks demonstrated noninferiority to eculizumab in two phase 3 trials. In regions where two PNH treatment options are available, it is important to consider patient preference. OBJECTIVE: The aim of this study was to assess patient preference for ravulizumab or eculizumab. METHODS: Study 302s (ALXN1210-PNH-302s) enrolled PNH patients who participated in the extension period of phase 3 study ALXN1210-PNH-302. In the parent study, eculizumab-experienced adult PNH patients received ravulizumab or eculizumab during a 26-week primary evaluation period. All patients in the extension period received ravulizumab. In study 302s, patient treatment preference was evaluated using an 11-item PNH-specific Patient Preference Questionnaire (PNH-PPQ©). Of 98 patients, 95 completed PNH-PPQ© per protocol for analysis. RESULTS: Overall, 93% of patients preferred ravulizumab whereas 7% of patients either had no preference (6%) or preferred eculizumab (1%) (P < 0.001). For specific aspects of treatment, ravulizumab was preferred (in comparison to no preference or eculizumab) on infusion frequency (98% vs. 0% vs. 2%), ability to plan activities (98% vs. 0% vs. 2%), and overall quality of life (88% vs. 11% vs. 1%), among other aspects. Most participants selected frequency of infusions as the most important factor determining preference (43%), followed by overall quality of life (23%). CONCLUSION: This study shows that a substantial proportion of patients preferred ravulizumab over eculizumab and provides an important patient perspective on PNH treatment when there is more than one treatment option.

Medical oncologist perspectives on palliative care reveal physician-centered barriers to early integration.

BACKGROUND: Early palliative care referral for patients with advanced cancer has demonstrable benefits but is underutilized. We sought to characterize medical oncologists' perceptions about palliative care referral in their clinical practices. METHODS: We conducted 4 focus groups with a national sample of medical oncologists to elicit perspectives about the optimal timing of and barriers to palliative care referral for patients with cancer. We used qualitative content analysis to uncover themes related to early integration of palliative care into standard oncologic practice. RESULTS: Study participants readily acknowledged the evidence supporting early palliative care referral. However, medical oncologists identified patient-centered and physician-centered barriers to widespread adoption of early palliative care. Patient-centered barriers included patients' and families' perceptions or misperceptions of the role of palliative care. Additionally, physicians themselves described acting as a barrier to palliative care referral because they were concerned that palliative care physicians may interfere with the plan of care, or offer options that were not endorsed by the medical oncologist. Medical oncologists depicted themselves having authority over the timing of palliative care referral, and as granting limited autonomy to other clinical team members in counseling patients about advanced care planning. CONCLUSIONS: Medical oncologists are hesitant to adopt the practice of early palliative care referral because they are concerned that other physicians may disrupt a patient's treatment plan. Physician-centered barriers may delay integration of palliative care, and future efforts to promote a collaborative approach to advanced care planning may improve patient-centered outcomes through access to early palliative care.

Development of the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) Medication Adherence Scale (PMAS).

Poor medication adherence is associated with reduced drug effectiveness, poor health-related quality of life, increased morbidity and mortality, and increased healthcare utilization and cost. Including the patient's voice is essential in understanding barriers to adherence. Useful patient-reported adherence measures are brief, inexpensive, non-invasive; can indicate barriers to adherence; and can be incorporated in electronic health records. The NIH Patient-Reported Outcomes Measurement Information System (PROMIS®) includes high-quality, freely available patient-reported measures covering many important constructs in patient-centered research but does not include a medication adherence measure. To fill this gap, we developed the PROMIS Medication Adherence Scale (PMAS) using the rigorous PROMIS instrument development guidelines. To develop the PMAS, we first conducted a review of the reviews, which enabled us to identify content areas relevant to medication adherence behavior. Then, we conducted qualitative research to elicit patients' views of and experiences with medication adherence. This process identified the following important content areas to guide item writing: extent medication is taken, knowledge of medication regimen, beliefs about medication, remembering to take medication, skipping due to side effects, skipping due to feeling better, and cost of medications. Based on the results of these activities, we wrote items and aimed to retain 1-2 items per content area. The final item set included 9 total adherence items, which were then refined through intensive comprehension and translatability review, as well as cognitive interviews. Future steps include testing the PMAS's validity.

Assessing Preferences for Rare Disease Treatment: Qualitative Development of the Paroxysmal Nocturnal Hemoglobinuria Patient Preference Questionnaire (PNH-PPQ©).

PURPOSE: To develop a patient preference questionnaire (PPQ) assessing eculizumab and ravulizumab treatment for paroxysmal nocturnal hemoglobinuria (PNH). PATIENTS AND METHODS: The development of the PNH-PPQ© was consistent with Food and Drug Administration guidelines for patient-reported outcome measure development, and included 1) a targeted literature review; 2) PNH expert clinician input on treatment preferences; 3) review of existing qualitative data on the PNH treatment and disease experience; 4) concept elicitation interviews with 8 PNH patients who received eculizumab and/or ravulizumab; 5) translatability review; and 6) cognitive debriefing with 5 patients. Interview participants were recruited through a United Kingdom PNH patient advocacy group and a Canadian clinical site involved in clinical trial ALXN1210-PNH-302. RESULTS: Six themes were identified as most relevant to the PNH treatment experience from the concept elicitation interviews: disease symptoms (n=8/8); treatment frequency (n=7/8); quality of life impact of treatment/disease (n=7/8); treatment burden (n=7/8); treatment efficacy (n=5/8); and treatment side effects (n=5/8). An initial list of 88 preference questions was reduced to 11 highly relevant and non-redundant questions reflecting the 6 themes. Cognitive interview participants unanimously agreed that the PNH-PPQ instructions were clear; response options were understandable, easy to use, and provided enough choices; and the questions captured the factors that inform treatment preferences. DISCUSSION: When new drugs have similar efficacy to existing medications, documenting patient preferences is important for confirming patient benefit from the new medication. Understanding what matters most to patients is essential for delivering patient-centered care and may play a particularly significant role in treatment decision making. The availability of such a tool may be especially important as new orphan drugs are developed and patients with rare diseases have more than one treatment option to consider. CONCLUSION: The PNH-PPQ provides a patient-centered approach for evaluating preferences for the treatment of PNH. The PNH-PPQ has subsequently assessed patient preference in the clinical trial sub-study ALXN1210-PNH-302s.

Neuropathy experienced by colorectal cancer patients receiving oxaliplatin: A qualitative study to validate the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity scale.

BACKGROUND: Although oxaliplatin is widely established as a standard treatment in colorectal cancer (CRC), oxaliplatin-induced neuropathy has emerged as a prominent dose-limiting side effect associated with quality of life decrements. Ongoing monitoring and management of neuropathy is important for CRC patient quality of life and adherence to treatment. Therefore, a validated self-reported measure of neuropathy would aid in the management and assessment of oxaliplatin-induced neuropathy in clinical practice and research. We sought to evaluate the content validity of the 13-item Functional Assessment of Cancer Therapy/Gynecologic Oncology Group- Neurotoxicity subscale (FACT/GOG-Ntx) for CRC patients receiving oxaliplatin. AIM: To understand the neuropathy experiences of CRC patients and assess content validity of the FACT/GOG-Ntx. METHODS: Semi-structured concept elicitation and cognitive debriefing interviews were conducted with 31 CRC patients experiencing peripheral neuropathy from current or previous oxaliplatin treatment. Interview data were analyzed using a constant comparative approach, and data were mapped to the FACT/GOG-Ntx to assess content validity. RESULTS: Mean age of the sample was 54 (range 34-82). The sample was primarily Caucasian (84%) and consisted of nearly equal numbers of men and women. Participants described 28 unique neuropathy symptoms; hand tingling (experienced by 87% of respondents); feet tingling (81%); hand numbness (68%); and feet numbness (84%) were most frequently mentioned. Neuropathy symptoms occurring on the feet were most often identified as most bothersome by participants. Eleven of the 13 FACT/GOG-Ntx items exhibited moderate to strong evidence of content validity. Two items related to trouble hearing and ringing in the ears had weak support; however, these items represent severe neuropathy and could be useful for a patient reported outcome measure. CONCLUSION: The FACT/GOG-Ntx represents the key neuropathy experiences of CRC patients treated with oxaliplatin.

Development, Validation, and Interpretation of the PROMIS Itch Questionnaire: A Patient-Reported Outcome Measure for the Quality of Life Impact of Itch.

Current patient-reported outcome measures for itch are limited and may not capture its full impact on health-related quality of life. We sought to develop, calibrate, and validate banks of questions assessing the health-related quality of life impact of itch as part of the Patient-Reported Outcomes Measurement Information System. A systematic process of literature review, content-expert review, qualitative research, testing in a sample of 600 adults, classical test theory methods, and item response theory analyses were applied. Exploratory and confirmatory factor analyses were followed by item response theory model and item fit analyses. Four itch-related item banks were developed: (i) general concerns, (ii) mood and sleep, (iii) clothing and physical activity, and (iv) scratching behavior. Item response theory and expert content review narrowed the item banks to 25, 18, 15, and 5 items, respectively. Validity of the item banks was supported by good convergent and discriminant validity with itch intensity, internal consistency, and no significant floor or ceiling effects. In conclusion, the Patient-Reported Outcomes Measurement Information System Itch Questionnaire banks have excellent measurement properties and efficiently and comprehensively assess the burden of itch.

Methodological challenges in conducting instrumentation research in non-communicative palliative care patients.

Well-designed, rigorously implemented instrumentation studies are essential to develop valid, reliable pain assessment tools in non-communicative (non-self-reporting) palliative care patients. When conducting a pain instrumentation study, a research team identified methodologic challenges surrounding informed consent, eligibility criteria, acute pain operational definitions, patient recruitment, missing data, and study-related training during a run-in phase at the beginning of the project and during the conduct of the study. The team dealt with these challenges through identifying root causes, implementing remedial measures, and collecting data to demonstrate improvement or resolution. Effective strategies included obtaining Institutional Review Board (IRB) approval for a waiver of informed consent, modifying eligibility criteria, ensuring that operational definitions and study procedures were consistent with clinical practice, decreasing time from screening to data collection to improve recruitment, increasing study nurse staffing by re-budgeting grant funds, focusing time and resources on high accruing clinical units, revising processes to minimize missing data, and developing detailed training for users of the instrument. With these multi-pronged solutions, the team exceeded the patient accrual target by 25% within the funding period and reduced missing data. While pain instrumentation studies in non-communicative patients have similar challenges to other palliative care studies, some of the solutions may be unique and several are applicable to other palliative care studies, particularly instrumentation research. The team's experience may also be useful for funders and IRBs.

Seizure burden in severe early-life epilepsy: Perspectives from parents.

OBJECTIVES: Seizure burden is typically measured by seizure frequency yet it entails more than seizure counts, especially for people with severe epilepsies and their caregivers. We aimed to characterize the multi-faceted nature of seizure burden in young people and their parents who are living with severe early-life epilepsies. METHODS: A one-day workshop and a series of teleconferences were held with parents of children with severe, refractory epilepsy of early-life origin and providers for children with epilepsy. The workshop sessions were structured as focus groups and aimed to identify components of seizure burden and their impact from the perspective of parents and providers. Data were gathered, organized, and refined during the workshop using an iterative 4-step process that drew upon grounded theory. RESULTS: Three primary components of seizure burden were identified: frequency, severity, and unpredictability, which was as important if not more important at times than frequency and severity. Caregivers noted that the impacts of seizures were experienced as acute-immediate consequences, longer-term consequences, and as chronic effects that develop and evolve over time. The severity of the child's neurological and medical status as well as where in the disease journey a family was represented additional contextual factors that influenced the experience of seizure burden. SIGNIFICANCE: Patient-reported and patient-centered outcomes are increasingly incorporated into the evaluation of treatment effectiveness. Without understanding how the disease creates burden for the patient (or family), it is difficult to know how to assess the impact of treatment. Our preliminary findings indicate seizure burden is a complex construct and unpredictability can be as important as frequency and severity.