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.

A mixed methods evaluation of patient perspectives on the implementation of an electronic health record-integrated patient-reported symptom and needs monitoring program in cancer care.

BACKGROUND: As cancer centers have increased focus on patient-centered, evidenced-based care, implementing efficient programs that facilitate effective patient-clinician communication remains critical. We implemented an electronic health record-integrated patient-reported symptom and needs monitoring program ('cPRO' for cancer patient-reported outcomes). To aid evaluation of cPRO implementation, we asked patients receiving care in one of three geographical regions of an academic healthcare system about their experiences. METHODS: Using a sequential mixed-methods approach, we collected feedback in two waves. Wave 1 included virtual focus groups and interviews with patients who had completed cPRO. In Wave 2, we administered a structured survey to systematically examine Wave 1 themes. All participants had a diagnosed malignancy and received at least 2 invitations to complete cPRO. We used rapid and traditional qualitative methods to analyze Wave 1 data and focused on identifying facilitators and barriers to cPRO implementation. Wave 2 data were analyzed descriptively. RESULTS: Participants (n = 180) were on average 62.9 years old; were majority female, White, non-Hispanic, and married; and represented various cancer types and phases of treatment. Wave 1 participants (n = 37) identified facilitators, including cPRO's perceived value and favorable usability, and barriers, including confusion about cPRO's purpose and various considerations for responding. High levels of clinician engagement with, and patient education on, cPRO were described as facilitators while low levels were described as barriers. Wave 2 (n = 143) data demonstrated high endorsement rates of cPRO's usability on domains such as navigability (91.6%), comprehensibility (98.7%), and relevance (82.4%). Wave 2 data also indicated low rates of understanding cPRO's purpose (56.7%), education from care teams about cPRO (22.5%), and discussing results of cPRO with care teams (16.3%). CONCLUSIONS: While patients reported high value and ease of use when completing cPRO, they also reported areas of confusion, emphasizing the importance of patient education on the purpose and use of cPRO and clinician engagement to sustain participation. These results guided successful implementation changes and will inform future improvements.

Protocol for a type 2 hybrid effectiveness-implementation study expanding, implementing and evaluating electronic health record-integrated patient-reported symptom monitoring in a multisite cancer centre.

INTRODUCTION: Cancer symptom monitoring and management interventions can address concerns that may otherwise go undertreated. However, such programmes and their evaluations remain largely limited to trials versus healthcare systemwide applications. We previously developed and piloted an electronic patient-reported symptom and need assessment ('cPRO' for cancer patient-reported outcomes) within the electronic health record (EHR). This study will expand cPRO implementation to medical oncology clinics across a large healthcare system. We will conduct a formal evaluation via a stepped wedge trial with a type 2 hybrid effectiveness-implementation design. METHODS AND ANALYSIS: Aim 1 comprises a mixed method evaluation of cPRO implementation. Adult outpatients will complete cPRO assessments (pain, fatigue, physical function, depression, anxiety and supportive care needs) before medical oncology visits. Results are available in the EHR; severe symptoms and endorsed needs trigger clinician notifications. We will track implementation strategies using the Longitudinal Implementation Strategy Tracking System. Aim 2 will evaluate cPRO's impact on patient and system outcomes over 12 months via (a) a quality improvement study (n=4000 cases) and (b) a human subjects substudy (n=1000 patients). Aim 2a will evaluate EHR-documented healthcare usage and patient satisfaction. In aim 2b, participating patients will complete patient-reported healthcare utilisation and quality, symptoms and health-related quality of life measures at baseline, 6 and 12 months. We will analyse data using generalised linear mixed models and estimate individual trajectories of patient-reported symptom scores at baseline, 6 and 12 months. Using growth mixture modelling, we will characterise the overall trajectories of each symptom. Aim 3 will identify cPRO implementation facilitators and barriers via mixed methods research gathering feedback from stakeholders. Patients (n=50) will participate in focus groups or interviews. Clinicians and administrators (n=40) will complete surveys to evaluate implementation. We will graphically depict longitudinal implementation survey results and code qualitative data using directed content analysis. ETHICS AND DISSEMINATION: This study was approved by the Northwestern University Institutional Review Board (STU00207807). Findings will be disseminated via local and conference presentations and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04014751; ClinicalTrials.gov.

Tracking dynamic changes in implementation strategies over time within a hybrid type 2 trial of an electronic patient-reported oncology symptom and needs monitoring program.

Background: Longitudinal tracking of implementation strategies is critical in accurately reporting when and why they are used, for promoting rigor and reproducibility in implementation research, and could facilitate generalizable knowledge if similar methods are used across research projects. This article focuses on tracking dynamic changes in the use of implementation strategies over time within a hybrid type 2 effectiveness-implementation trial of an evidence-based electronic patient-reported oncology symptom assessment for cancer patient-reported outcomes in a single large healthcare system. Methods: The Longitudinal Implementation Strategies Tracking System (LISTS), a timeline follow-back procedure for documenting strategy use and modifications, was applied to the multiyear study. The research team used observation, study records, and reports from implementers to complete LISTS in an electronic data entry system. Types of modifications and reasons were categorized. Determinants associated with each strategy were collected as a justification for strategy use and a potential explanation for strategy modifications. Results: Thirty-four discrete implementation strategies were used and at least one strategy was used from each of the nine strategy categories from the Expert Recommendations for Implementing Change (ERIC) taxonomy. Most of the strategies were introduced, used, and continued or discontinued according to a prospective implementation plan. Relatedly, a small number of strategies were introduced, the majority unplanned, because of the changing healthcare landscape, or to address an emergent barrier. Despite changing implementation context, there were relatively few modifications to the way strategies were enacted, such as a change in the actor, action, or dose. Few differences were noted between the trial's three regional units under investigation. Conclusion: This study occurred within the ambulatory oncology clinics of a large, academic medical center and was supported by the Quality team of the health system to ensure greater uptake, uniformity, and implementation within established practice change processes. The centralized nature of the implementation likely contributed to the relatively low proportion of modified strategies and the high degree of uniformity across regions. These results demonstrate the potential of LISTS in gathering the level of data needed to understand the impact of the many implementation strategies used to support adoption and delivery of a multilevel innovation. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04014751, identifier: NCT04014751.

Validation of brief symptom indexes among patients with recurrent or metastatic squamous cell carcinoma of the head and neck: A trial of the ECOG-ACRIN Cancer Research Group (E1302).

BACKGROUND: Patients with advanced head and neck cancer have identified pain, fatigue, and difficulties swallowing, breathing, and communicating as high-priority disease-related symptoms. The Functional Assessment of Cancer Therapy-Head and Neck Symptom Index-10 (FHNSI-10) assesses these symptoms. We sought to validate the FHNSI-10, another brief symptom index (FHNSI-7), and individual symptom endpoints representing these high-rated priority disease symptoms among patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). METHODS: Patients (N = 239) were enrolled in a phase III randomized clinical trial (E1302) and completed the FHNSI-10 at multiple time points. We assessed the internal consistencies and test-retest reliabilities of the FHNSI-10 and FHNSI-7 scores, and the known-groups validity, predictive criterion validity, and responsiveness-to-change of the symptom indexes and individual symptom endpoint scores. RESULTS: The FHNSI-10 and FHNSI-7 indexes showed satisfactory internal consistencies (Cronbach's alpha coefficient range 0.60-0.75) and acceptable test-retest reliabilities (intraclass correlation coefficients = 0.75 and 0.74, respectively). The FHNSI-10, FHNSI-7, and the pain, fatigue, swallowing, and breathing symptom scores showed evidence of known-groups validity by performance status at baseline. The FHNSI-10, FHNSI-7, and the pain, fatigue, and breathing symptom scores at baseline showed evidence of predictive criterion validity for overall survival, but not time-to-progression (TTP). Changes in the symptom indexes and individual symptom scores were not associated with changes in performance status over 4 weeks, though most patients had stable performance status. CONCLUSIONS: There is initial evidence of validity for the FHNSI-10 and FHNSI-7 indexes and selected individual symptom endpoints as brief disease-related symptom assessments for patients with recurrent or metastatic SCCHN.

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.

Development of a Functional Assessment of Chronic Illness Therapy item library and primary symptom list for the assessment of patient-reported adverse events associated with immune checkpoint modulators.

AIM: To develop a comprehensive item library of patient-reported, immunotherapy-related adverse events (irAEs) that draws from and expands on the Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System. METHODS: Literature review and iterative expert input. Based on a literature review of irAEs, we developed a framework of immunotherapy classes and their associated symptoms. Clinical experts then reviewed iterations of symptom summaries and item maps linked to the immunotherapy framework. Experts provided content review and feedback was shared across experts until consensus was reached. The iterative process facilitated creation of a Primary Symptom List associated with immune checkpoint modulators (ICMs), drawn from the larger set of symptoms. Existing FACIT items were mapped to the symptom list, and new items were written as needed to create the item library. RESULTS: The full item library of irAEs is comprised of 239 items, covering 142 unique symptoms across 75 inflammatory reactions/immune conditions. A subset of 66 items comprises a Primary Symptom List considered most common/relevant to ICM treatment. This includes gastrointestinal, skin, pulmonary, neurologic, musculoskeletal, and multiple miscellaneous and constitutional symptoms. CONCLUSION: The FACIT Immunotherapy Item Library is a compilation of 239 self-report items that capture the wide range of AEs experienced by people receiving immune treatments. A subset of 66 items comprises a Primary Symptom List meant for ICM therapy. Use of items selected from this library is encouraged in clinical research and clinical practice evaluation.

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.

Measuring the concerns of cancer patients with low platelet counts: the Functional Assessment of Cancer Therapy--thrombocytopenia (FACT-Th) questionnaire.

PURPOSE: The specific concerns of people with low platelet counts (thrombocytopenia) have not been characterized well in the literature and as a result proper measurement of patient-reported concerns is lacking. We report on the development and validation of questions specifically targeted to patients with thrombocytopenia that can be added to the more general concerns in the Functional Assessment of Cancer Therapy-General. MATERIALS AND METHODS: An 18-item FACT-Thrombocytopenia Subscale (ThS) was rated and evaluated by thrombocytopenic patients at baseline during a validation study of 40 thrombocytopenic and 43 nonthrombocytopenic cancer patients. To evaluate responsiveness, patients completed a battery of self-report measures including the FACT-Th and were followed up for change in platelet count over 2 weeks. RESULTS: All subscales and aggregated scores showed high internal consistency at initial assessment and at retesting. Convergent and divergent validity were demonstrated by predicted relationships between FACT-Th subscales and mood, mental and physical component scores of the SF-36, and social desirability. The ThS differentiated patients with low platelets from those with normal platelet counts and good performance from poor performance status patients. CONCLUSION: The FACT-Th is a reliable and valid measure for assessing the impact of thrombocytopenia on patients' lives. It can distinguish cancer patients with and without thrombocytopenia and is responsive to increase in platelet count over time. The FACT-Th may therefore prove useful as a measure of self-reported symptoms and concerns related to thrombocytopenia in clinical trials evaluating new pharmacologic agents and/or platelet transfusion practice.