Preferences for Accessing Patient Reported Outcomes and Health Information Among Thrombotic Thrombocytopenic Purpura Survivors

Introduction: Our previous qualitative studies of immune-mediated thrombotic thrombocytopenic purpura (iTTP) survivors revealed that patients did not communicate to their hematologists about residual cognitive and fatigue issues. A way to overcome this communication barrier is implementation of patient-reported outcomes (PROs) in routine care. Integration of PROs into the clinical care of other diseases has resulted in improved patient-provider communication, symptom management, quality of life and overall patient satisfaction. However, decisions about the mode of administration are challenging. Although 92% of the United States population has access to the internet, studies have shown minorities prefer alternative modes of administration. Given that iTTP disproportionately affects Black women, understanding patient preference is critical for integrating PRO instruments into routine care. The primary study goal was to determine the preferred mode of administration of PRO instruments in iTTP. Furthermore, many individuals use the internet as a source of medical information/advice. A study of iTTP literacy reported that only 34% of survivors correctly identified disease relapse risk factors suggesting a critical knowledge gap. A secondary goal was to describe iTTP survivors' behaviors regarding using the internet for medical information or support. Methods: We utilized a cross-sectional study design. iTTP survivors were recruited from August 2019 until present. Eligibility included: 1) age >18 years, 2) documented ADAMTS13 deficiency (< 10% activity) at diagnosis or during a relapse and 3) > 1-year clinical remission. Multi-center recruitment of survivors included: Oklahoma University, Ohio State University, University of Minnesota, Johns Hopkins University, University of Rochester, University of Pennsylvania, University of Alabama at Birmingham, University of Utah and the University of Vermont. Following informed consent, survivors were administered the PROMIS ® cognitive function ability, anxiety and fatigue instruments via their preferred mode (online, telephone, or self-administered). Typical internet usage, behaviors regarding searching for health information online and demographics were also obtained. Results: To date, 94 survivors have completed the study (83% female; 54% White; 34% Black; median age 49 years [range 26-85 years]). A majority (54%) preferred completing PROMIS ® surveys online vs. self-administered or telephone administered. However, among Black survivors, only 38% preferred online administration and among survivors aged ≥65 years only 22% preferred online administration. Interestingly, there was an overall shift in a preference toward online administration following the onset of the COVID-19 pandemic (45% (21/47) preferred online pre vs 66% (31/47) preferred online post). Ninety-one percent (86/94) of survivors reported at least occasional internet use vs 8 (9%) reported none. Similarly, 82% (70/85) had searched the internet for health/medical information for themselves in the past year. Also 62% (53/86) of the survivors selected 'strongly agree' or 'agree' to the statement that the internet helps them determine if symptoms are important enough to see a doctor. Likewise, 62% used the internet to interpret doctor's recommendations. Additionally, 47% (40/86) 'strongly agree/agree' the internet helped determine if they would take a medication/seek alternative treatment. Moreover, 64% (55/86) agreed the internet was a good way to find others experiencing similar health problems. However, when asked about behaviors over the past year, only 42% (36/85) used online social networking sites like Facebook to look for health information or find others with iTTP and only 36% (31/85) had actually participated in online iTTP support groups. Conclusions: Overall iTTP survivors preferred online PRO administration; however, Black and older survivors preferred other methods. Recognizing these preferences is a vital step toward integrating PROs into routine care. Furthermore, iTTP survivors are using the internet as a source of medical support and information. Therefore, it is critical to not only educate iTTP survivors about credible online resources but also to create additional content. Also, future studies are needed to further explore the impact of the COVID-19 pandemic on online health behaviors. Disclosures Terrell: Sanofi: Consultancy; Takeda: Consultancy. Journeycake: HEMA Biologics: Honoraria; LFB: Honoraria. Mazepa: Answering TTP Foundation: Research Funding; Sanofi Aventis: Other. Cuker: Spark Therapeutics: Research Funding; Sanofi: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Novo Nordisk: Research Funding; Novartis: Research Funding; Bayer: Research Funding; Alexion: Research Funding; UpToDate: Patents & Royalties; Synergy: Consultancy. Chaturvedi: Dova: Other: Advisory board member; UCB: Other: Advisory board participation; Argenx: Other: Advisory board member; Alexion: Other: Advisory board member; Sanofi Genzyme: Other: Advisory board member. Lim: Hema Biologics: Honoraria; Sanofi Genzyme: Honoraria; Dova Pharmaceuticals: Honoraria. Gangaraju: Alexion: Consultancy; Sanofi Genzyme: Consultancy. Cataland: Alexion: Consultancy, Research Funding; Sanofi Genzyme: Consultancy; Ablynx/Sanofi: Consultancy, Research Funding; Takeda: Consultancy.

Comparing the use of patient-reported outcomes in clinical studies in Europe in 2008 and 2018: a literature review

Purpose Several guidelines for the use of patient-reported outcomes (PROs) in clinical studies have been published in the past decade. This review primarily aimed to compare the number and compliance with selected PRO-specific criteria for reporting of clinical studies in Europe using PROs published in 2008 and 2018. Secondarily, to describe the study designs, PRO instruments used, patient groups studied, and countries where the clinical studies were conducted. Methods A literature search was conducted in MEDLINE to identify eligible publications. To assess the number of publications, all abstracts were screened for eligibility by pairs of reviewers. Compliance with PRO-specific criteria and other key characteristics was assessed in a random sample of 150 eligible full-text publications from each year. Randomized controlled trials (RCTs) were assessed according to the full CONSORT-PRO checklist. Results The search identified 1692 publications in 2008 and 4290 in 2018. After screening of abstracts, 1240 from 2008 and 2869 from 2018 were clinical studies using PROs. By full-text review, the proportion of studies discussing PRO-specific limitations and implications was higher in 2018 than in 2008, but there were no differences in the other selected PRO-specific criteria. In 2018, a higher proportion of studies were longitudinal/cohort studies, included ≥ 300 patients, and used electronic administration of PRO than in 2008. The most common patient groups studied were those with cancer or diseases of the musculoskeletal system or connective tissue. Conclusion The number of clinical studies from Europe using PROs was higher in 2018 than in 2008, but there was little difference in compliance with the PRO-specific criteria. The studies varied in terms of study design and PRO instruments used in both publication years.

Quality of life and patient-reported outcome measures

To improve or sustain patients’ quality of life (QoL) is the main goal of palliative care. In palliative care as in healthcare in general, QoL is commonly conceptualized as health-related quality of life (HRQoL) which is the self-perceived health status of an individual and encompasses measurable components that are related to health, disease, illness, and medical interventions. Patient-reported outcome (PRO) measures is the term presently used for any measure that collects responses directly from the patients and includes measures on QoL, HRQoL, functions, and symptoms. In spite of substantial evidence on the positive outcomes of using PRO instruments (questionnaires) in the clinic, such use still faces barriers from the health system and the healthcare providers. The content and the measurement capabilities of present PRO instruments can also be a barrier. The selection of PRO instruments is recommended to follow a sequential approach. Define overall aim(s), define the research question(s), agree upon the key outcome(s), and select the appropriate set of questions/questionnaires guided by the primary and secondary outcomes. In general, it is recommended to use a generic or a disease-specific questionnaire and supplement with domain-specific questionnaire(s) for measurement of fatigue, pain, anxiety, depression, or other symptoms/functions reflecting the purpose(s) of the data collection.

Development of a preliminary conceptual model of the patient experience of chronic kidney disease: a targeted literature review and analysis

Background Patient-reported outcome (PRO) instruments should capture the experiences of disease and treatment that patients consider most important in order to inform patient-centred care and product development. The aim of this study was to develop a preliminary conceptual model of patient experience in chronic kidney disease (CKD) based on a targeted literature review and to characterize existing PRO instruments used in CKD. Methods PubMed, EMBASE and Cochrane databases and recent society meetings were searched for publications reporting signs/symptoms and life impacts of CKD. Concepts identified in the literature review were used to develop a preliminary conceptual model of patient experience of CKD, overall, and within patient subpopulations of differing CKD causes, severities and complications. PRO instruments, identified from PRO databases, CKD literature and CKD clinical trials, were assessed for content validity, psychometric strength and coverage of concepts in the literature review. Results In total, 100 publications met criteria for analysis; 56 signs/symptoms and 37 life impacts of CKD were identified from these sources. The most frequently mentioned signs/symptoms were pain/discomfort (57% of publications) and tiredness/low energy/lethargy/fatigue (42%); the most commonly reported life impacts were anxiety/depression (49%) and decrements in physical functioning (43%). Signs/symptoms and life impacts varied across the subpopulations and were more frequent at advanced CKD stages. The preliminary conceptual model grouped signs/symptoms into seven domains (pain/discomfort; energy/fatigue; sleep-related; gastrointestinal-related; urinary-related; skin−/hair−/nails-related; and other) and life impacts into six domains (psychological/emotional strain; cognitive impairment; dietary habit disruption; physical function decrements; interference with social relationships; and other). Eleven PRO instruments were considered to be promising for use in CKD; all had limitations. Conclusions Although preliminary, the proposed conceptual model highlights key PROs for people with CKD and is intended to spur development of more tailored PRO instruments to assess these concepts.

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

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.

Psychometric properties of patient reported outcome (PRO) instruments in patients with small cell lung cancer (SCLC) in RESILIENT part 1.

e24027 Background: The ongoing two-part phase 2/3 RESILIENT study (NCT03088813) is investigating the efficacy and safety of liposomal irinotecan monotherapy in patients with SCLC who have progressed on or after first line platinum-based chemotherapy. This exploratory analysis from RESILIENT part 1 was conducted to confirm the psychometric properties of established PRO instruments that had not previously been validated in patients with SCLC. Methods: Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) Core 30 (C30) and the EORTC QLQ Lung Cancer 13 (LC13) before treatment assignment (baseline), every 6 weeks thereafter, at treatment discontinuation and at the 30-day follow-up visit. Psychometric methods included descriptive statistics (items and scales), correlations (item-to-item and item-to-total), internal consistency (Cronbach’s α), test-retest reliability (intraclass correlation coefficient [ICC], two-way random effects model), construct validity and sensitivity to change. The analysis included patients who received at least one dose of study drug and completed at least one PRO assessment. Results: Thirty patients were enrolled in RESILIENT part 1 and included in the analysis. At baseline, 68% of patients reported ‘not severe’ or ‘mild’ symptoms. Floor effects (i.e. more than 25% of responses of ‘not at all’) were observed for several of the functioning/impact and symptom scales of the EORTC QLQ C30 and LC13. Moderate to strong correlations were found among most questionnaire items within their respective scales. Acceptable evidence for internal consistency and good test-retest reliability were observed. Selected results for the EORTC QLQ LC13, including dyspnea scales, are shown in the Table. The magnitude of correlations among PRO instruments supported evidence for convergent validity in this sample. Conclusions: In RESILIENT part 1, patients experienced low and tolerable symptoms at enrollment, limiting the potential for further improvement. Overall, these PRO instruments had acceptable psychometric properties (e.g. construct validity, reliability and ability to detect change) in this sample. However, these analyses should be repeated in a larger sample using data from RESILIENT part 2. Clinical trial information: NCT03088813. [Table: see text]

Patient-reported outcomes in clinical trials for multiple myeloma: Where we are.

e18615 Background: It is recommended to include patient-reported outcomes (PROs) in cancer trials to ensure clinical benefit based on patients’ perceptions. For multiple myeloma patients, PRO measurement is essential to understand the impact of treatment on their physical and psychosocial functional behaviour. However, it is unclear which PRO instruments are utilized in multiple myeloma trials, how often they are used and whether results are consistently reported. The aim of this project was to explore the use and frequency of PRO instruments in randomized controlled trials for multiple myeloma and to assess the consistency of their reporting. Methods: Within the European Hematology Association (EHA) project to develop guidelines for the use of PROs in adult patients with hematological malignancies, MEDLINE and CENTRAL were systematically searched for randomized controlled trials investigating multiple myeloma between 2015 and 2020. Study design, disease and treatment characteristics, the primary outcome and used PRO instrument(s) were extracted using a pre-defined template. To assess the consistency of PRO reporting, study registries were compared with publications, study protocol and Health Technology Assessment (HTA) reports where available. Results: Overall, 10,707 records were found. Following screening for randomized-controlled trials, 283 ongoing, completed or published studies were included for review. 118 studies planned the use of PROs. The most frequently used PRO instrument (92 studies) was the EORTC QLQ-30, an instrument that measures health-related quality-of-life (HRQoL) in cancer patients. The disease-specific questionnaire EORTC-MY20 was also frequently used (50 studies). Likewise, the HRQoL instrument EQ-5D was used in 50 studies. Overall, 38 different PRO instruments were reported. In 39 studies for which a study protocol was found, only 19 reported PRO instruments consistently with the trial registry for the study. In addition, in 30 studies, for which a publication reported PRO results (58 overall), the information on PRO instruments differed between publication and the trial registry. For example, PRO instruments mentioned in the registry were omitted in the respective publications. Additionally, information on PRO in HTA reports was available for 26 studies, of which 18 reports were consistent with the trial registries. Conclusions: The results show that measurement of PROs still remain under-utilized in multiple myeloma research. While most PRO instruments identified in this review comply with the recommendations for incorporating PROs into clinical research in adult oncology, they are often inconsistently reported. Thus, reporting standards for the use of PROs are needed to ensure consistency in the use and reporting of PROs.

Fundamental Outcome Measurement: Selecting Patient Reported Outcome Instruments and Interpreting the Data they Produce

Over the past 40 years literally thousands of generic and disease specific patient reported outcome (PRO) instruments have been developed. While most were developed for a specific study and were never used again, there is still the question of how manufacturers and others should select a PRO instrument for a study. These studies may be clinical pivotal trials or observational tracking studies to support therapy response. Formulary committees also need to be able to interpret PRO data to make decisions about whether to accept claims for therapy response. It is possible to argue that the many different approaches to outcome measurement have resulted from the lack of agreed methodologies. However, a more likely explanation is that the authors have failed to apply the axioms of fundamental measurement when creating their measures. The result is a plethora of ordinal PRO instruments that inform little about the impact of interventions. Clinical trials rarely report PRO data. Where they do, analyses are generally restricted to (for example) changes in the experimental group’s scores. Comparisons between the treatment and placebo groups or between active groups are infrequently reported, most likely due to the failure of the instrument to show differences or changes in outcome. This is unfortunate as it means no assessment is made of the value that patients gain from the intervention. This commentary is intended to make researchers and formulary committees aware of the issues that need to be addressed when selecting PRO instruments for a study or evaluating publications and claims for therapy response. The latter is crucial as reported data influence the selection of medicines and healthcare products. In the latter case a particular concern is with PRO claims embedded in simulation models.

A Systematic Literature Review of the Burden of Central Nervous System Complications for Patients with Sickle Cell Disease

INTRODUCTION: Sickle cell disease (SCD), a complex genetic blood disorder involving multicellular interactions between blood and endothelial cells, is often accompanied by central nervous system (CNS) complications. Effects range from silent cerebral infarct (SCI) to abnormal blood flow, and consequent overt stroke. This study assessed the humanistic and economic burden associated with CNS complications in patients with SCD and identified patient-reported outcome (PRO) instruments for future research. METHODS: MEDLINE, Embase, Cochrane CENTRAL/CDSR and 11 congresses were searched to identify English language studies published from January 2000 to May 2020 and screened with predefined criteria by two independent researchers. Clinical trials (CT) or observational studies assessing humanistic burden, economic burden, or instruments used to measure burden in patients with SCD and CNS complications (N≥15) were included. Humanistic burden was broadly defined to include quality of life (QoL), symptoms and function. RESULTS: Of the 3194 articles identified, 34 were included. Study designs were 29% retrospective observational (10/34), 29% cross-sectional (10), 26% prospective (9), 9% randomized CT (3), and 6% systematic reviews (2). Study size varied widely (16-4,485 patients with SCD and CNS complications). 77% (26) focused on pediatric patients. Separately, 77% (26) were in a US setting. Overt stroke (12), stroke and SCI (11), or SCI only (7) were the most frequently described CNS complications. Twenty-five studies reported on humanistic burden, 18 of which measured cognitive function using the Wechsler Intelligence Scales. A significant decrease was reported in full scale (FS) (stroke vs. no stroke: 73.5 vs. 84.7; P=.04), verbal (abnormal vs. normal MRI: 74.1 vs. 84.6; P=.02), and performance IQ (stroke vs. no stroke: 69.5 vs. 81.5; P=.02) for patients with overt strokes or SCI compared to non-stroke SCD controls. Greater impairment was reported for overt stroke compared with SCI (multivariate meta-analysis of mean IQ difference: -10.3; P=.0013). In addition to stroke/SCI, socio-environmental factors (i.e., family income level, lack of college education) were significantly associated with a decrease in IQ (P=.005 and P=.023, respectively). Five studies assessed motor function, reporting significantly impaired function for patients with stroke compared to non-stroke SCD controls (Purdue Pegboard both hands: 7.5 vs. 10.1; P=.0001). Among children with SCD who had experienced their first stroke, those receiving hydroxyurea (HU) for prevention of recurrent stroke had significantly less moderate to severe motor disability (physician assessed) than children not receiving HU (23.1 vs. 88.9%; P<.001). Nine studies reported economic outcomes related to healthcare resource use (HCRU) (8) and direct costs (5). HCRU and cost to manage CNS complications are high, with a median LOS of 5 days (IQR 3-9) and median hospitalization charges of $18,956 (2012 USD) for patients with SCD and stroke. Treatment costs were also substantial in patients with SCI, with annual transfusion plus chelation costs ranging between $18,149 and $67,361/year (2016 USD). No studies reported indirect costs. While many studies used clinician-administered performance outcome (PerfO) measures such as the Wechsler Scales, only 1 study employed a PRO instrument: the Children's Depression Index. In addition to the Wechsler Scales, PerfO measures of cognitive function included the Woodcock-Johnson Psychoeducational Battery (6 studies), Children's Memory Scale (4), and California Verbal Learning Test for Children (4). CONCLUSIONS: This systematic review found that SCD patients with CNS complications often experience diminished cognitive/motor function and incur substantial costs. In particular, the mean FSIQ for SCD patients with stroke and SCI was reported to be 'extremely low' to 'low' (65.9 to 83.6) and 'low' to 'average' (77.2 to 95.9), respectively across studies. The Wechsler Scales were the most commonly used PerfO measure of cognitive function, while use of disease-specific PRO instruments was extremely limited. Given that the majority of published data focuses on children, future research is needed to evaluate the burden of disease for SCD adults with CNS complications, and to assess patient perspectives and QoL to better quantify aspects of burden beyond cognitive performance. Disclosures Lee: Novartis Pharmaceuticals Corporation: Current Employment. Nellesen:Analysis Group, Inc.: Consultancy. Lucas:Analysis Group, Inc.: Consultancy. Paulose:Novartis Pharma AG: Current Employment.

Development and psychometric evaluation of the assessment of self-injection questionnaire: an adaptation of the self-injection assessment questionnaire

Background Patient-reported outcome (PRO) instruments provide robust and effective means of evaluating patients’ treatment experience; however, none adequately cover experience using self-injection devices with enhanced features, such as an electromechanical autoinjector (e-Device). The aim of this study was to develop a PRO instrument that accurately assesses patient experience of using an e-Device and to evaluate its psychometric properties. Methods A mixed-methods approach was taken; two parallel, targeted literature reviews were conducted to identify relevant concepts and existing self-injection PRO instruments that could be adapted. Patient feedback obtained from two focus groups was used to inform initial instrument development. The pilot instrument was then administered in a multicenter, open-label, phase 3 clinical study in which patients self-injected certolizumab pegol using an e-Device, to gather evidence of its psychometric qualities. Exit interviews were conducted with a sub-sample of patients enrolled in the study to confirm the appropriateness and clarity of the items included and cognitively debrief the instrument. Confirmatory factor analysis (CFA) was conducted on all items, and each domain’s internal consistency was measured using Cronbach’s ɑ. Results The literature searches identified several e-Device-specific concepts related to device features, device function, side effects/reactions/pain, confidence, and interference/convenience in daily life. Seven existing PRO instruments were identified. The Self-Injection Assessment Questionnaire (SIAQ), containing pre- and post-injection questionnaire modules, was selected as most suitable and adapted using feedback from 19 patients in the two focus groups to form the pilot Assessment of Self-Injection (ASI) questionnaire. CFA resulted in some changes to the grouping of items in the post-injection module domains following psychometric evaluation of the ASI. Internal consistency was satisfactory for all pre- and post-injection domains (ɑ > 0.8). Cognitive debriefing results from 12 patient exit interviews confirmed the ASI’s appropriateness and clarity. Conclusions The ASI was developed iteratively with patient input and was evaluated in its intended clinical context of use. Psychometric analyses indicated promising cross-sectional results; the ASI was well understood and considered relevant by patients self-injecting using the e-Device, suggesting that it could be used in real-world settings to aid with clinical decision making. Trial registration: NCT03357471