scholarly journals Development of a Cold Agglutinin Disease-Specific Patient-Reported Outcome Symptom Measure

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4057-4057
Author(s):  
Florence Joly ◽  
Pronabesh Dasmahapatra ◽  
Jun Su ◽  
Dana DiBenedetti ◽  
Katherine Kosa ◽  
...  
Keyword(s):  
Conceptual Model ◽  
Patient Perspective ◽  
Patient Reported Outcome ◽  
Cold Agglutinin ◽  
Cognitive Debriefing ◽  
Shortness Of Breath ◽  
Item Pool ◽  
Cold Agglutinin Disease ◽  
Publicly Traded ◽  
Patient Reported

Abstract Introduction Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia in which red blood cells are bound by cold agglutinin autoantibodies. In addition to cold-induced symptoms, patients with CAD experience symptoms of chronic anemia and hemolysis including fatigue, weakness, and shortness of breath (Swiecicki PL et al. Blood 2013;122(7):1114-21). The objectives of this study were to identify disease-related symptoms and impacts most important to patients with CAD, and to evaluate whether existing patient-reported outcome (PRO) measures are appropriate to assess relevant CAD concepts. Methods As part of a larger study, qualitative concept elicitation (CE) interviews were conducted to better understand the disease burden of CAD from the patient perspective. The results from the first set of interviews were reported by Su J et al. Blood 2020;136(1):29-30. Based on the identified symptoms and impacts, standard survey methodological principles were used to develop a draft item pool to address concepts of interest. Items were refined and evaluated during the second set of interviews, which included 3 rounds of 60-minute phone interviews with patients with CAD using a semi-structured interview guide that included a CE section and cognitive debriefing. Pooled results from both sets of interviews were used to develop a conceptual model of the symptoms and impacts of CAD. Physician advisors were also invited to review the concepts identified in the interviews and to select those that they believed were most relevant as part of an advisory board. A PubMed review of literature published between 2010-2020 was also conducted to identify existing PRO measures used in the assessment of symptoms, impacts, and/or quality of life and patient experiences in adults with CAD or similar disease areas. Identified PRO measures were assessed to determine the extent to which they captured CAD-specific concepts identified in the CE interviews. Results In total, 37 participants diagnosed with primary or secondary CAD took part in the interviews (Set 1, n=16; Set 2, n=21). Overall, the mean age of participants was 67.2 years (range: 35-87), and the majority were female (73%). The most frequently reported symptom of CAD was reactions to cold environments (n=36; 97%), e.g., cold or numb feet/hands, and skin discoloration. Other reported symptoms included fatigue (n=35; 95%), shortness of breath (n=28; 76%), and trouble with thinking/concentration (n=21; 57%). The most frequently reported unfavorable impact of CAD was on day-to-day activities (n=32; 87%). Other negative impacts included effects on enjoyable activities (n=29; 78%) e.g., gardening, physical health/activities (n=28; 76%), social/leisure life (n=26; 70%); and mood/emotions (n=24; 65%). Most participants (n=30; 81%) reported they had made lifestyle/behavioral changes to help limit their CAD symptoms, such as wearing extra clothing in places that were likely to be cold. A conceptual model of the symptoms and impacts of CAD was developed based on these data (Figure 1). Physician advisors (n=7) agreed that the patient-reported symptoms and impacts identified during the interviews were relevant concepts to CAD. Following a literature review, no existing PRO measure was found to adequately address concepts deemed critical to CAD from the patient perspective. Owing to the lack of an existing fit-for-purpose measure, 14 concepts were identified from the interviews to develop an initial draft item pool. During the cognitive debriefing in the second set of interviews, participants (n=21: Round 1 n=8; Round 2 n=7; Round 3 n=6) evaluated these concepts. After 3 rounds of interviews, the new item set yielded 11 items relating to: fatigue; cold sensitivity; dyspnea; wearing extra clothing; limited physical, social, and enjoyable activities; difficulty with usual activities; mood; frustration; and anxiety/stress. Participants reported these items were comprehensive of their experiences with CAD, easy to understand, and would be relevant to gaining a better understanding of individuals' experiences with CAD. Conclusion These results support the need for a novel PRO measure(s) that adequately addresses concepts critical to the measurement of CAD symptoms and impacts from the patient perspective. Figure 1 Figure 1. Disclosures Joly: Sanofi: Current Employment. Dasmahapatra: Sanofi: Current Employment, Current equity holder in publicly-traded company. Su: Sanofi: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Astellas US LLC: Current Employment. DiBenedetti: RTI Health Solutions: Current Employment, Other: Employee of RTI Health Solutions, funded by Sanofi Genzyme to conduct the original work which this abstract is based on. Kosa: RTI Health Solutions: Current Employment. Hill: Novartis: Consultancy, Honoraria; Grifols: Consultancy, Honoraria; Sanofi: Consultancy; ReAlta: Consultancy; Alexion: Honoraria; Amgen: Honoraria; Argenx: Consultancy; Apellis: Consultancy, Honoraria.

scholarly journals P116 Development of a new patient-reported outcome measure for patients with complex cryptoglandular fistulas

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S208-S209
Author(s):  
J McCurdy ◽  
P Crooks ◽  
C Gwaltney ◽  
R Krupnick ◽  
K A Cadogan ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Literature Review ◽  
Conceptual Model ◽  
Rating Scale ◽  
Daily Life ◽  
Patient Reported Outcome ◽  
Cognitive Debriefing ◽  
Item Pool ◽  
Patient Reported

Abstract Background Complex cryptoglandular fistulas (CCF) arise from infected anal glands and are often associated with substantial morbidity and healthcare utilization. Standarized patient-reported outcome measures (PROMs) for CCF are lacking. Thus, we aimed to develop a disease-specific PROM to assess the burden of symptoms and their impact on daily life in patients with CCF. Methods To develop a conceptual model, a targeted literature review was conducted to identify symptoms and impacts on daily life associated with CCF. Existing PROMs relating to anal fistulas were also sought. Semi-structured interviews with colorectal surgeons (n=5) assessed clinical perspectives on patient experience of CCF. A draft item pool was developed based on the refined conceptual model and using the Quality of Life in Patients with Anal Fistula Questionnaire as a reference. The tool was refined through concept elicitation interviews on the symptoms and impacts of CCF, and cognitive debriefing on the interpretation, understanding and response to each item. Interviews were conducted until concept saturation was achieved and patient feedback suggested no further refinements were required. Results The literature review identified discharge, pain, faecal incontinence and bleeding as the most prevalent symptoms, and embarrassment as the most prevalent impact on daily life. Results from surgeon interviews were then used to revise the initial conceptual model. Twenty US adults (60% female; mean age, 49 years) with clinically confirmed CCF participated in interviews (four waves of n=5). Patients identified 10 salient symptoms and 11 salient impacts on daily life (salient defined as mention by ≥50% of patients and mean disturbance rating ≥5 on a 10-point scale). The final conceptual model included the main symptoms and treatment-related effects, and impacts on daily life. The draft item pool was refined, resulting in a final PROM consisting of 14 items (covering frequency and severity) relating to symptom domains – discharge, incontinence, pain, irritation, odour, abscess – and 6 items relating to health-related quality of life domains – functional, physical, psychological, social health. The PROM features a 7-day recall period, with responses mostly given on a 5-point verbal rating scale. Cognitive debriefing confirmed that the PROM was clear, easy to understand and relevant to patients’ experiences. Conclusion The 20-item CCF questionnaire (CCFQ-20) is a new PROM that has been developed and tested for content validity, following expert guidance and regulatory best practices. It addresses a comprehensive set of salient symptoms and impacts experienced by patients with CCF. Psychometric testing is required to fully evaluate this PROM. Sponsor: Takeda Pharmaceuticals USA, Inc.

scholarly journals Qualitative interviews to improve patient-reported outcome measures in late-onset Pompe disease: the patient perspective

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Alaa Hamed ◽  
Kristina An Haack ◽  
Chad Gwaltney ◽  
Eileen Baranowski ◽  
Andrew Stewart ◽  
...  
Keyword(s):  
Literature Review ◽  
Conceptual Model ◽  
Pompe Disease ◽  
Patient Perspective ◽  
Late Onset ◽  
Qualitative Interviews ◽  
Patient Reported Outcome ◽  
Patient Interviews ◽  
Patient Interview ◽  
Patient Reported

Abstract Background Late-onset Pompe Disease (LOPD) is a rare, heterogeneous disease manifested by a range of symptoms varying in severity. Research establishing the frequency of these symptoms and their impact on patients’ daily lives is limited. The objective of this study was to develop a conceptual model that captures the most relevant symptoms and functional limitations experienced by patients with LOPD, to inform the development of new patient-reported outcome (PRO) tools. Methods A preliminary conceptual model was constructed following a literature review and revised through interviews with expert clinicians to identify important and relevant concepts regarding symptoms and impacts of LOPD. This preliminary model informed the development of a qualitative patient interview guide, which was used to gather the patient perspective on symptoms and impacts relating to LOPD or its treatment (including symptom/impact frequency and levels of disturbance). Patient interviews aided further refinement of the conceptual model. The findings from the patient interviews were triangulated with the literature review and clinician interviews to identify the most relevant and significant effects of LOPD from the patient perspective. Results Muscle weakness, fatigue, pain, and breathing difficulties (especially while lying down) were the most common and highly disturbing symptoms experienced by patients. Limitations associated with mobility (e.g., difficulty rising from a sitting position, getting up after bending) and activities of daily living, (e.g., reduced ability to participate in social/family activities or work/study) were the most frequently reported impacts with the highest levels of disturbance on the patient’s daily life. These identified symptoms and impacts were included in the new conceptual model of disease. Conclusions This qualitative patient interview study, also informed by a literature review and clinician interviews, identified the most frequent and relevant symptoms and the functional impact of LOPD on patients. The study interviews also captured the patient-preferred language to describe symptoms and impacts of LOPD. The results from this study can be used to develop future PRO instruments that are tailored to the specific symptoms and impacts experienced by patients with LOPD.

scholarly journals Understanding the patient experience in hepatocellular carcinoma: a qualitative patient interview study

2021 ◽  
Author(s):  
Nikunj Patel ◽  
Joshua Maher ◽  
Xandra Lie ◽  
Chad Gwaltney ◽  
Afsaneh Barzi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Development ◽  
Conceptual Model ◽  
Patient Experience ◽  
Outcome Measurement ◽  
Qualitative Interviews ◽  
Patient Reported Outcome ◽  
Weight Changes ◽  
Patient Reported ◽  
Pro Instruments

Abstract Purpose This study aimed to elucidate the patient experience of hepatocellular carcinoma (HCC) to guide patient-centered outcome measurement in drug development. Methods Patients with HCC participated in qualitative interviews to elicit disease-related signs/symptoms and impacts, using discussion guides developed from literature searches and discussions with oncologists. Interview participants rated the disturbance of their experiences (0–10 scale). A conceptual model was developed and mapped against patient-reported outcome (PRO) instruments identified from database reviews. Results Interviews were conducted with 25 individuals with HCC (68% were men; median age: 63 years; 12% Barcelona clinic liver cancer (BCLC) stage A; 32% stage B; and 56% stage C) in the USA. Fifty-one HCC-related concepts were identified from the interviews and were grouped into eight sign/symptom categories (eating behavior/weight changes; extremities [arms, legs]; fatigue and strength; gastrointestinal; pain; sensory; skin; other) and four impact categories (emotional; physical; cognitive function; other) for the conceptual model. The most prevalent and disturbing experiences across the disease stages were fatigue/lack of energy and emotional impacts such as frustration, fear, and depression. Abdominal pain and skin-related issues were particularly common and disturbing in individuals with HCC stage C. The EORTC QLQ-C30 and HCC18 were identified as commonly used PRO instruments in HCC studies and captured the relevant signs/symptoms associated with the patient experience. Conclusion Patients with HCC reported a range of signs/symptoms and impacts that negatively affect daily functioning and quality of life. Including PRO measures in HCC clinical trials can provide meaningful patient perspectives during drug development.

scholarly journals Development of a conceptual model and patient-reported outcome measures for assessing symptoms and functioning in patients with heart failure

2020 ◽  
Vol 29 (10) ◽  
pp. 2835-2848
Author(s):  
Olga Moshkovich ◽  
Katy Benjamin ◽  
Katie Hall ◽  
Ryan Murphy ◽  
Robyn von Maltzahn ◽  
...  
Keyword(s):  
Heart Failure ◽  
Literature Review ◽  
Conceptual Model ◽  
Phase 1 ◽  
Patient Reported Outcome Measures ◽  
Patient Reported Outcome ◽  
Cognitive Testing ◽  
Expert Interviews ◽  
Cognitive Changes ◽  
Patient Reported

Abstract Purpose Heart failure (HF) is a common condition that places considerable burden on patients. We aimed to develop a patient-reported outcome (PRO) measure to assess the symptoms and impacts of HF. Methods Phase 1: a targeted literature review, expert interviews, and concept elicitation (CE) interviews with patients with HF (n = 26) were used to develop a conceptual model of the core symptoms and impacts of HF. To capture these concepts, three new fit-for-purpose PRO questionnaires were constructed in accordance with US Food and Drug Administration PRO guidance. Phase 2: three ‘waves’ of cognitive interviews were conducted with patients with HF (n = 28) to validate and refine the questionnaires. Results Three key symptoms—shortness of breath, oedema, and fatigue—were identified across the literature review, expert interviews and CE interviews. Several additional symptoms, cognitive changes and impacts of HF were reported in the CE interviews and included in the conceptual model. A 10-item symptom questionnaire (Heart Failure-Daily Symptom Diary) was constructed; cognitive testing showed that the final PRO measure was easy to understand/complete and relevant to patients with HF, confirming content validity. Two HF impact questionnaires were developed (Assessing Dyspnoea’s Impact on Mobility and Sleep and Heart Failure-Functional Status Assessment), but required refinement to ensure patient understanding. Conclusions Patient input contributed to the development of a PRO instrument for assessing physical and cognitive symptoms important to patients with HF using novel measurement strategies. Inclusion of daily metrics offers differentiation from other qualified instruments and may provide clinical insight for improving lifestyles. Additionally, two draft PRO measures may, after further validation, be useful to assess the impacts of HF.

Long-Term Efficacy of the Terminal Complement Inhibitor Eculizumab in a Patient with Cold Agglutinin Disease (CAD)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2882-2882
Author(s):  
Alexander Roeth ◽  
Andreas Huettmann ◽  
Ulrich Duehrsen ◽  
Thomas Philipp
Keyword(s):  
Complement System ◽  
Previous Treatment ◽  
The Body ◽  
Cold Agglutinin ◽  
Complement Factor ◽  
Cold Agglutinin Disease ◽  
Autoantibody Production ◽  
Transfusion Requirements ◽  
Patient Reported ◽  
Terminal Complement

Abstract Cold agglutinin disease (CAD) is a rare form of autoimmune hemolysis in which monoclonal or polyclonal IgM autoantibodies can activate the complement system in colder areas of the body (e.g. extremities), resulting in red blood cell destruction. Typically prednisone is ineffective and, although chemotherapy is often used, only on rare occasions does it suppress autoantibody production. Although CAD is often mild and self-limited, some cases require hospitalization and can be life-threatening. Supportive transfusions of red blood cells may also be necessary. Based on what is known about the pathophysiology of CAD, blockade of the terminal complement cascade by eculizumab could be a possible therapeutic approach. Eculizumab, a monoclonal antibody targeting complement factor C5, has shown high efficacy in patients with hemolytic paroxysmal nocturnal hemoglobinuria (PNH) through inhibition of the terminal complement system. We tested the efficacy of eculizumab in a transfusion-dependent patient with CAD refractory to extensive previous treatment. Eculizumab was dosed as follows: 600 mg IV every 7±2 days × 4; 900 mg 7±2 days later; and then 900 mg every 14±2 days. The patient has continued dosing for approximately one year. As eculizumab treatment may increase the risk for meningococcal disease, a standard vaccination scheme was administered prior to treatment. Transfusion requirements as well as clinical and biochemical indicators of hemolysis were monitored. Our results showed that intravascular hemolysis, measured by lactate dehydrogenase (LDH), was reduced by 46% from 780±50.5 U/L (mean±SE) during the 1 year period prior to treatment to 446±35.5 U/L during 1 year of eculizumab treatment. Reduction in hemolysis resulted in improvement of anemia (from a mean hemoglobin level of 10.0 g/dL 1 year prior to treatment to 11.8 g/dL during 1 year of eculizumab treatment) with a significant reduction in the number of PRBC units transfused (from a mean of 18 units during the pre-treatment period to 0 units during eculizumab treatment). Ferritin levels also decreased from 666±70.8 μg/L (mean±SE) before treatment to 313±8.9 μg/L during treatment. The patient reported an improvement of fatigue and overall quality of life. There were no adverse events observed and the ongoing therapy with eculizumab continues to be safe and well tolerated in this patient. In summary, this is the first report of eculizumab efficacy in a patient with CAD. Chronic blockade of terminal complement with eculizumab resulted in reductions in hemolysis and transfusion requirements and improvements in anemia and fatigue. As no alternative effective treatment options are available, these promising results provide a rationale for a clinical trial for the use of eculizumab in patients with CAD.

AL Amyloidosis: Development Of a Conceptual Model and a Symptom Diary

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5609-5609
Author(s):  
Emuella Flood ◽  
David Seldin ◽  
Ai-Min Hui ◽  
Deborah Berg ◽  
Huamao Mark Lin
Keyword(s):  
Conceptual Model ◽  
Research Funding ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Cognitive Debriefing ◽  
Concept Elicitation ◽  
Wide Range ◽  
Patient Reported ◽  
Symptom Diary ◽  
Patients Perspective

Abstract Introduction Amyloidosis is a very rare blood disease characterized by the production of abnormal misfolded extracellular proteins that are deposited in body tissues or organs, leading to organ dysfunction. The most common form is systemic light chain (AL) amyloidosis. With no cure, treatment is directed at suppressing development of the abnormal protein, correcting or stabilizing organ function, and managing symptoms. Very little research has been done to assess patients’ symptoms in this disease and how they may be mitigated by available therapies.  The first objective of this study was to understand the symptoms and impact of the disease and treatment from the patients’ perspective. This insight was used to develop a comprehensive conceptual model of AL amyloidosis.  A second objective was to confirm the content of a draft amyloidosis symptom diary and provide recommendations to refine the measure. Methods Three data sources were included in this study: 1) A literature review using OvidSP (includes MEDLINE and Embase)using disease-specific and quality of life search terms; 2) An internet search to identify blogs (online diaries) written by patients about their disease/treatment experience; and 3) One-on-one telephone interviews with adult AL amyloidosis patients. Patients were recruited through physician referral and by the Amyloidosis Foundation. Eligible and interested patients were mailed an informed consent form and study questionnaires. Using a standardized guide, a trained interviewer conducted a concept elicitation interview to explore experiences of living with AL amyloidosis, after which the patient completed the symptom diary and underwent a cognitive debriefing interview.  The cognitive debriefing was designed to explore patient understanding of each instruction, item, and response option. Interview transcripts were coded to identify key concepts and themes emerging from the data using qualitative data analysis software, MaxQDA. Results Of 270 English language abstracts identified and reviewed, 10 articles appeared to include a patient-reported outcome (PRO) measure and were selected for full review. Nine patient blogs were identified and reviewed. Symptoms identified from the literature and from patient blogs informed the development of a draft symptom measure. Ten patients participated in the concept elicitation / cognitive debriefing interviews (mean age, 61 years, SD=8; 70% male). Eight reported experience with chemotherapy, 6 reported having received a stem cell transplant, and one had received a heart transplant. Patients identified symptoms as being related to both the disease and/or treatments.  Symptoms reported by at least 30% of the sample included fatigue (100%), weakness (100%), shortness of breath (90%), neuropathy (90%), edema (100%), dizziness/lightheadedness (80%), decreased/lack of appetite (60%), diarrhea (50%), constipation (40%), and difficulty sleeping (30%). Ninety-four percent of codes had been applied by the 7th interview, and only one new code (“heartburn”) was applied in the last interview, suggesting that key symptom concepts were identified with this sample. A conceptual model illustrating the various impacts of disease and treatment was developed.  Findings from cognitive debriefing interviews revealed that overall, patients found the diary to be straightforward and easy to complete. Most patients reported that the symptoms included in the measure adequately captured their experiences with AL amyloidosis. However, feedback suggested that certain symptoms such as swelling in the upper body, needed clarification. Conclusions A comprehensive conceptual model of symptoms and impacts of disease and treatment was developed and could be used to identify important outcomes from the patients’ perspective that should be assessed in clinical trials to capture treatment benefit.  AL amyloidosis is associated with a wide range of symptoms related to location of amyloid deposits, as well as side effects related to the treatment administered.  Despite this variability, a core set of symptoms emerged and a draft diary capturing symptoms likely to be applicable to most patients was developed. Based on the feedback from the cognitive debriefing interviews, patients found the diary to be straightforward and easy to complete.  Additional research and use in trials can provide further evidence for the validity and reliability of the diary. Disclosures: Seldin: Celgene: Research Funding; Prothena: Research Funding; Amyloidosis Foundation: Membership on an entity’s Board of Directors or advisory committees. Hui:Millennium: The Takeda Oncology Company: Employment. Berg:Millennium: The Takeda Oncology Company: Employment. Lin:Millennium: The Takeda Oncology Company: Employment.

Standards for evaluating patient-reported outcome (PRO)-based performance measures.

2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 45-45
Author(s):  
Ethan M. Basch ◽  
Christine Goertz ◽  
Keri Christenson ◽  
Amaris Crawford ◽  
R. Adams Dudley ◽  
...  
Keyword(s):  
Performance Improvement ◽  
Performance Measures ◽  
Patient Reported Outcomes ◽  
Patient Perspective ◽  
Patient Reported Outcome ◽  
Lessons Learned ◽  
Use Cases ◽  
Use Case ◽  
Patient Reported ◽  
Measurement Strategies

45 Background: There is growing interest to use performance measures that integrate patient-reported outcomes (PROs), but there are no existing methodological standards for developing, implementing, or analyzing such measures in this context. Methods: To develop standards for evaluating PRO-based performance measures submitted to or developed by the American Medical Association-convened Physician Consortium for Performance Improvement, a multi-disciplinary expert technical panel was assembled. A systematic literature review and landscape overview were conducted to identify use cases and existing PRO standards in related contexts. Lessons learned from use cases and existing standards guided development of discrete methodological standards. Results: The systematic review identified only one use case, whereas the landscape overview identified eight. Five purposes were identified for which PROs might be measured to assess performance, including one categorized as process and four as outcome. Eight discrete methodological standards were developed which will be detailed at the meeting. Conclusions: The patient perspective is an essential but missing component of performance evaluation. When appropriately elicited, data from patients can be informative. Lack of adherence to good practices and inadequate patient input when developing measurement strategies are potential pitfalls to be avoided.

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