Clinically Important Change in SF-12v2 Physical (PCS) and Mental (MCS) Component Summary Scores for Patients with Cold Agglutinin Disease: An Analysis Using the Phase 3 CARDINAL and CADENZA Studies

Abstract Introduction Cold Agglutinin Disease (CAD) is an autoimmune condition resulting in hemolytic anemia; the subsequent fatigue causes a reduction in patient's physical and mental health-related quality of life (HRQoL). Sutimlimab (formerly BIVV009) is a humanized monoclonal anti-C1s antibody with a clinical trial program to support its development as a treatment for CAD. CARDINAL (NCT03347396) and CADENZA (NCT03347422) are Phase 3 clinical trials that assessed the treatment-related change in HRQoL using the 12-item Short-Form Health Survey (version 2) (SF-12v2) in patients with CAD treated with sutimlimab. This analysis aimed to estimate the clinically important change (CIC) in SF-12v2 physical (PCS) and mental (MCS) component summary scores, using pooled data from CARDINAL and CADENZA. Methods CARDINAL was an open-label, single-arm, multicenter study for patients with CAD with a recent blood transfusion. CADENZA was a randomized, double-blind, placebo-controlled, multicenter study; patients with CAD (without a recent blood transfusion) were randomized 1:1 to receive sutimlimab or placebo. In both studies, patients underwent efficacy and safety assessments for 6 months (Part A). Data from the Part A 26-week component of both studies were combined for these analyses. CIC, defined as mean score change divided by SD at baseline, gave treatment effect sizes of 0.2 (small), 0.5 (moderate) or 0.8 (large), allowing for interpretation of patient-reported outcomes by pre-determining clinically meaningful improvements in physical and mental well-being. Anchor- and distribution-based analyses were performed to estimate the CIC for the following patient-reported outcome measures: Patient Global Impression of (fatigue) Severity (PGIS) and Patient Global Impression of Change (PGIC). Anchor-based approaches (mean change and model-based) examined the relationship between change in SF-12v2 PCS and MCS scores and change in related anchor variables: change in PGIS, PGIC (from baseline to Week 26) and hemoglobin levels (g/dl) (from baseline to the mean value of Weeks 23, 25 and 26). The independent variable was change in PCS and MCS scores and dependent variables were binary (improvement vs. no improvement) in model-based analyses. Results Fifty-five patients with SF-12v2 data available were included from CARDINAL (n=17) and CADENZA (n=38). The median (range) age was 70 (46-88) years and 76% of patients were female (n=42). Mean (SD) PCS and MCS scores at baseline were 40.9 (7.8) and 47.3 (9.1), respectively. From baseline to Week 26, mean (SD) changes in PCS and MCS scores were 4.1 (7.1) and 3.1 (11.6), respectively. Correlations between changes in PCS and MCS scores and PGIS, hemoglobin, and self-report of change in PGIC at Week 26 ranged from 0.36 to 0.55, indicating moderate associations (Table 1). When using an anchor-based approach that evaluated mean change in PCS and MCS scores, CIC estimates ranged from 2.9 to 7.4 for PCS and 2.2 to 7.0 for MCS (Table 2). Results from the 2 model-based anchor approaches, which estimated CIC using receiver operating characteristic curves and an adjusted logistic regression-based approach ranged from 2.0 to 7.3 for PCS and 1.1 to 4.1 for MCS (Table 2). Distribution-based analyses determined the CIC to be 3.9 and 4.6 for PCS and MCS, respectively, when based on one-half of the standard deviation of baseline scores, and 3.5 (PCS) and 4.1 (MCS) when based on the standard error of measurement. The median estimate produced by all anchor-based methods were closely aligned with results of distribution-based analyses. Therefore, taking into consideration all approaches, the median CICs for CAD patients for PCS and MCS were 3.9 and 2.8, respectively. Conclusion In this analysis, patients with CAD had median CIC values of 3.9 and 2.8 for PCS and MCS, respectively. In a previous study, anchor-based analyses for the general population gave CIC scores of 3.0 for both PCS and MCS (Maruish ME et al. 3 rd edition; Lincoln, RI; 2012). The results of this study converge well with those estimates observed for the general population involving thousands of observations. This analysis also demonstrated that meaningful physical and mental health benefits (including a reduction in fatigue) were associated with improvements in hemoglobin levels, a main clinical outcome measure of CAD. Figure 1 Figure 1. Disclosures Joly: Sanofi: Current Employment. Kosinski: QualityMetric Incorporated, LLC: Current Employment. Shafer: Sanofi: Current Employment, Current equity holder in publicly-traded company; Pfizer: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months. Wardecki: Sanofi: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Other: May hold shares and/or stock options with Sanofi. Karaouni: BMAPS SARL(Geneva, Switzerland): Current Employment; Sanofi: Consultancy. Hill: Amgen: Honoraria; Alexion: Honoraria; ReAlta: Consultancy; Sanofi: Consultancy; Grifols: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Argenx: Consultancy; Apellis: Consultancy, Honoraria.

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Work Status, Missed Time at Work, Work Performance, and Quality of Life in Adult Survivors of Hematopoietic Cell Transplant in Childhood

Blood ◽

10.1182/blood-2021-148750 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3049-3049

Author(s):

Neel S. Bhatt ◽

Akasha K. Palou Torres ◽

Judith Myers ◽

Rachel Phelan ◽

Bronwen E. Shaw

Keyword(s):

Physical Function ◽

Work Performance ◽

Pain Interference ◽

Work Status ◽

Cell Transplant ◽

Publicly Traded ◽

Hematopoietic Cell Transplant ◽

The Past ◽

Patient Reported

Abstract Background: Post-allogeneic hematopoietic cell transplant (HCT) work status is an important indicator of survivors' health recovery and social and economic well-being. However, current literature lacks data on work status, missed time at work, work performance, and quality of life (QOL) of long-term survivors of childhood HCT. Methods: A cross-sectional web-based survey study of ≥1-year survivors of childhood allogeneic HCT (performed between 1985-2010 at Children's Wisconsin, Milwaukee, WI) who were <18 years of age at HCT and ≥18 years of age at their most recent assessment. Eligible survivors were identified using the Center for International Blood and Marrow Transplant Research database and contacted by email and/or mail. Validated patient reported outcomes measures, the World Health Organization Health and Work Performance Questionnaire (HPQ) and the National Institutes of Health Patient Reported Outcomes Measurement Information System (PROMIS) were used to capture work and QOL data, respectively. Using HPQ responses, working survivors' work absenteeism and presenteeism scores were calculated. Absenteeism scores were also calculated for the survivors who reported to be students. Absolute absenteeism was defined as 4*(no. of hours expected at work or school) - no. of hours actually worked or attended school. Relative absenteeism was defined as absolute absenteeism score/ 4*(no. of hours expected at work or school). Absolute presenteeism was defined as 10*(self-reported work performance in last 4 weeks). Relative presenteeism was defined as self-reported work performance in last 4 weeks / self-reported performance of co-workers. Higher absenteeism and presenteeism scores indicated higher missed time at work or school and better work performance, respectively. PROMIS domains were scored on a T-score metric with a mean score of reference population at 50 and standard deviation of 10. The primary outcome was individual PROMIS domain score as a continuous variable. Univariate linear regression was performed to study factors associated with increase in PROMIS domain scores. For negatively worded domains (anxiety, depression, fatigue, sleep disturbance, cognitive concerns, pain interference), higher score was considered worse and for positively worded domains (physical function, satisfaction with social roles and activities), lower score was considered worse. Student survivors were considered employed in the analysis. P-value <0.05 was considered statistically significant. Results: Out of 99 allogeneic HCT recipients who met the selection criteria, 47 initiated the survey and 44 completed it (44% response rate). At the time of survey, 73% (n=32) of the respondents were working, 23% (n=10) were unemployed, and 4% (n=2) were students. Median age at HCT and survey were 11.1 years (interquartile range [IQR] 7.0-13.5) and 30.0 years (IQR 26.5-34.0), respectively. Median follow-up from HCT was 22 years (range 9-32). Fifty two percent were females and 75% received HCT for malignant diseases (acute lymphoblastic leukemia 45%). Compared to unemployed survivors, employed survivors reported less pain interference and sleep disturbance (Figure 1). History of acute graft vs. host disease (GVHD) was associated with worse physical function. Median absolute absenteeism and presenteeism scores were 0 hours (IQR [-1.5]-16) and 83 (IQR 73-92), respectively. Higher absolute presenteeism was associated with less pain interference and more satisfaction with social roles and activities and physical function. Higher relative presenteeism was associated with less cognitive concerns. Higher absolute absenteeism was associated with less depression and higher relative absenteeism with less fatigue (Table 1). Conclusions: Nearly a quarter of the survivors reported being unemployed at the time of the survey. Significant associations between survivors' work status, work performance, and QOL were identified. Our findings provide an important insight on the implications of work outcomes on HCT survivors' physical, mental, and social health and emphasizes the importance of routine longitudinal assessment of work status, performance and QOL in this population. These results also have the potential to help develop effective communication strategies with employers to balance work expectations of survivors in order to achieve better work productivity and in turn, good QOL. Figure 1 Figure 1. Disclosures Bhatt: Johnson & Johnson: Divested equity in a private or publicly-traded company in the past 24 months; Moderna, Inc.: Divested equity in a private or publicly-traded company in the past 24 months; Pfizer Inc.: Divested equity in a private or publicly-traded company in the past 24 months; Rite Aid Corporation: Divested equity in a private or publicly-traded company in the past 24 months. Phelan: Amgen Pharmaceuticals: Research Funding. Shaw: mallinkrodt: Other: payments; Orca bio: Consultancy.

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Eptinezumab for the prevention of chronic migraine: efficacy and safety through 24 weeks of treatment in the phase 3 PROMISE-2 (Prevention of migraine via intravenous ALD403 safety and efficacy–2) study

The Journal of Headache and Pain ◽

10.1186/s10194-020-01186-3 ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Stephen Silberstein ◽

Merle Diamond ◽

Nada A. Hindiyeh ◽

David M. Biondi ◽

Roger Cady ◽

...

Keyword(s):

Chronic Migraine ◽

Patient Reported Outcomes ◽

Controlled Study ◽

Efficacy And Safety ◽

Phase 3 ◽

Double Blind ◽

Patient Global Impression ◽

Calcitonin Gene ◽

Patient Reported ◽

Global Impression Of Change

Abstract Background PROMISE-2 was a phase 3, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of repeat intravenous (IV) doses of the calcitonin gene-related peptide–targeted monoclonal antibody eptinezumab (ALD403) for migraine prevention in adults with chronic migraine. This report describes the results of PROMISE-2 through 24 weeks of treatment. Methods Patients received up to two 30-min IV administrations of eptinezumab 100 mg, 300 mg, or placebo separated by 12 weeks. Patients recorded migraine and headache endpoints in a daily eDiary. Additional assessments, including patient-reported outcomes, were performed at regularly scheduled clinic visits throughout the 32-week study period (screening, day 0, and weeks 2, 4, 8, 12, 16, 20, 24, and 32). Results A total of 1072 adults received treatment: eptinezumab 100 mg, n = 356; eptinezumab 300 mg, n = 350; placebo, n = 366. The reduction in mean monthly migraine days observed during the first dosing interval (100 mg, − 7.7 days; 300 mg, − 8.2 days; placebo, − 5.6 days) was further decreased after an additional dose (100 mg, − 8.2 days; 300 mg, − 8.8 days; placebo, − 6.2 days), with both doses of eptinezumab demonstrating consistently greater reductions from baseline compared to placebo. The ≥50% and ≥ 75% migraine responder rates (MRRs) increased after a second dose, with more eptinezumab-treated patients experiencing migraine response than placebo patients (≥50% MRRs weeks 13–24: 100 mg, 61.0%; 300 mg, 64.0%; placebo, 44.0%; and ≥ 75% MRRs weeks 13–24: 100 mg, 39.3%; 300 mg, 43.1%; placebo, 23.8%). The percentages of patients who improved on patient-reported outcomes, including the Headache Impact Test and Patient Global Impression of Change, increased following the second dose administration at week 12, and were greater with eptinezumab than with placebo at all time points. No new safety concerns were identified with the second dose regarding the incidence, nature, and severity of treatment-emergent adverse events. Conclusion Eptinezumab 100 mg or 300 mg administered IV at day 0 and repeated at week 12 provided sustained migraine preventive benefit over a full 24 weeks and demonstrated an acceptable safety profile in patients with chronic migraine. Trial registration ClinicalTrials.gov (Identifier: NCT02974153). Registered November 23, 2016.

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P096 Subjective ratings of medication strength of lemborexant over 6 months in subjects with moderate or severe insomnia

SLEEP Advances ◽

10.1093/sleepadvances/zpab014.140 ◽

2021 ◽

Vol 2 (Supplement_1) ◽

pp. A52-A52

Author(s):

C Drake ◽

J Yardley ◽

K Pinner ◽

M Moline

Keyword(s):

Severity Index ◽

Subjective Ratings ◽

Phase 3 ◽

Double Blind ◽

Patient Global Impression ◽

Insomnia Disorder ◽

Patient Reported ◽

Positive Effect ◽

Insomnia Severity

Abstract Introduction In Study 303 (SUNRISE-2), significantly more subjects reported a positive effect of lemborexant (LEM), a dual orexin receptor antagonist, versus placebo (PBO) on their sleep at 1mo, 3mo and 6mo, as assessed by items 1–3 of the Patient Global Impression–Insomnia (PGI-I). LEM-treated subjects also reported larger and statistically significant decreases in the Insomnia Severity Index (ISI) versus PBO. This analysis examined potential LEM tolerance via patient-reported ratings of medication strength on PGI-I item 4 in subjects with moderate/severe insomnia. Methods In this 12mo double-blind, PBO-controlled (first 6mo), phase 3 study, subjects ≥18y with insomnia disorder and ISI scores ≥15 were randomized to PBO (n=318) or LEM (5mg, [LEM5], n=316; 10mg, [LEM10], n=315). The ISI and PGI-I were administered at 1mo, 3mo and 6mo. Results The percentage of subjects with moderate (ISI=15–21; n=692) or severe (ISI=22–28; n=223) insomnia at baseline who rated LEM as “just right” increased from 1mo (moderate: LEM5=46.4%; LEM10=43.3%; PBO=31.3%; severe: LEM5=35.8%; LEM10=40.6%; PBO=15.0%) to 6mo (moderate: LEM5=56.5%; LEM10=53.9%; PBO=39.7%; severe: LEM5= 54.8%; LEM10=55.4%; PBO=21.6%). Ratings of “too weak” decreased over 6 months in both ISI severity groups. PBO group ratings of “too weak” always exceeded the LEM groups by >15%. Ratings of “too strong” were low and stable over time. Conclusions Findings suggest that LEM tolerance does not occur over 6mo with either LEM dose since patient perceptions of LEM treatment being “too weak” did not increase over the study period. These data support the persistent efficacy of long-term LEM treatment for chronic insomnia.

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PAIN AND FUNCTION ONE YEAR AFTER DECOMPRESSIVE DISC SURGERY: CASES AUGMENTED WITH THE DIAM INTERSPINOUS IMPLANT VERSUS THOSE RECEIVING MICRODISCECTOMY

Journal of Musculoskeletal Research ◽

10.1142/s0218957712500133 ◽

2012 ◽

Vol 15 (02) ◽

pp. 1250013 ◽

Cited By ~ 1

Author(s):

R. J. Crawford ◽

J. M. Lynn ◽

Q. Malone ◽

R. I. Price

Keyword(s):

Nucleus Pulposus ◽

Important Change ◽

Leg Pain ◽

Repeat Surgery ◽

Patient Reported ◽

Patient Groups ◽

Clinically Significant ◽

One Year ◽

Clinically Important Change ◽

Herniated Nucleus Pulposus

Purpose: To examine clinical outcomes after decompressive lumbar surgery for herniated nucleus pulposus (HNP) in two cohorts from a single surgeon: Microdiscectomy alone [MICRO] versus microdiscectomy augmented with the Device for Intervertebral Assisted Motion [DIAM™, Medtronic Sofamor Danek, Memphis, USA]. We hypothesized that DIAM-augmented microdiscectomy would provide superior outcomes to microdiscectomy alone given purported benefits for interspinous devices reported in the literature. Improvements would concur with clinically significant change. Methods: Two separate HNP patient groups were sourced from a single surgeon: MICRO [n = 47 (17F/30M); 45 years (SD 14.2; 22–75)] and DIAM [n = 29 (10F/19M); 42 years (SD 11.2; 20–64)]. Patient-reported outcomes for function [MICRO=Roland-Morris Questionnaire (RMQ); DIAM=Oswestry Disability Index (ODI)] and back and leg pain [visual analogue scale (VAS)] were serially examined at preoperative baseline, 4–6 weeks, 6 and 12 months postoperatively. Incidence of repeat surgery at the index segment was recorded. Data were reported using descriptive statistics, unpaired t-tests and repeated ANOVA (Scheffe's post-hoc test). Statistically meaningful differences were defined by p < 0.05. Results: MICRO cases had higher preoperative leg pain (by 19%; p < 0.01). Improvements in absolute function and leg pain at one year were better in the MICRO group (p < 0.01). Both groups showed clinically significant improvement for all variables at each time-point during the period of follow-up. MICRO cases had proportionally fewer repeat surgeries (3/47 versus 4/29). Conclusions: Significant improvements in function, back and leg pain were shown in both patient groups out to one year. Clinically important change to function, back and leg pain was achieved for the MICRO cases, while clinically important change to leg pain occurred in the DIAM group. MICRO cases required proportionally fewer repeat surgeries by one year postoperatively. Microdiscectomy augmented with DIAM did not result in superior outcomes in treatment of herniated nucleus pulposus compared with microdiscectomy alone.

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Reporting of patient reported outcome (PRO) in clinical trials: A systematic review of clinical trials.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.6590 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 6590-6590 ◽

Cited By ~ 1

Author(s):

Liat Vidal-Fisher ◽

Laura Vidal Boixader ◽

Vasily Andrianov ◽

Kelly Kevelin Curtis ◽

Daniel Shepshelovich ◽

...

Keyword(s):

Clinical Trials ◽

Randomized Trials ◽

Patient Reported Outcome ◽

Phase 3 ◽

The Past ◽

Patient Reported ◽

Oncology Clinical Trials ◽

Eortc Qlq C30 ◽

Eortc Qlq

6590 Background: Clinically relevant outcomes as improvements in overall survival (OS) or quality of life (QOL) should guide decision-making. The FDA encourages the implementation of patient-centric measures in clinical trials. Over the past decade a growing number of protocols have included PROs in their outcome measures. We aimed to evaluate the frequency at which PRO measures, incorporated into clinical trials, are made publicly available, when trial results are published. Methods: We searched Citeline Trialtrove database, a registry of clinical trials, for randomized phase 3 trials of patients with non-small cell lung cancer (NSCLC), recruiting during 2006-2016, with PRO listed. We excluded trials evaluating supportive treatment, and those unpublished. We identified publications associated with the trial, and extracted various parameters, including whether or not PRO outcome was published. Results: Of 158 NSCLC trials identified, 99 listed at least 1 PRO. 24 trials were excluded (supportive care, unpublished). The commonly used scales were EORTC-QLQ C30, QLQ-LC13, LCSS, FACT-L, and EQ-5D. Study sponsor was industry in 45 trials, and industry-academic in 12 trials. Of 75 trials analyzed, 41 (55%) published the results of the PRO endpoint. Only 37% of the 75 included a comprehensive report of PRO, and many publications referenced the PRO briefly. Of 41 trials that reported PRO, only 21 (51%) provided information about missing PRO data. 59 trials were published as full-text, of which 40 (68%) reported the PRO, and 53% reported the PRO more than 6 months after the initial full publication. Of the trials that showed PFS benefit, with no OS benefit, 22/34 (65%) published the results of the PRO endpoints. Conclusions: Despite a growing emphasis on QOL and the inclusion of PROs in oncology clinical trials, and despite patient and healthcare provider efforts to record PRO data, a significant number of NSCLC randomized trials do not report the PRO. The collection of PRO data should result in routine, timely and appropriate reporting as part of the trial outcome publication, to allow for a thorough assessment of investigational clinically relevant treatment effect.

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Risk Mitigation Strategy for Concizumab Clinical Trials after Pause Due to Non-Fatal Thrombotic Events

Blood ◽

10.1182/blood-2020-139563 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 40-40

Author(s):

Stephanie Valer Seremetis ◽

Katarina Cepo ◽

Josephine Skovgaard Rasmussen ◽

Trine Høyer Rose ◽

Søren Tamer ◽

...

Keyword(s):

Clinical Trials ◽

Risk Mitigation ◽

Mitigation Strategies ◽

Publicly Traded ◽

Private Company ◽

Phase 3 ◽

Pivotal Phase ◽

Thrombotic Risk ◽

The Past ◽

Trial Protocols

Introduction Concizumab, a humanized recombinant monoclonal antibody directed against the tissue factor pathway inhibitor, is under investigation as a subcutaneous prophylactic treatment for patients with hemophilia A or B (HA/HB) with and without inhibitors. In the concizumab phase 2 trials, treatment was well tolerated and a favorable safety profile was shown, with no deaths or thromboembolic events and no adverse events (AEs) leading to withdrawal. We describe the non-fatal thrombotic serious AEs (SAEs) that occurred during the pivotal phase 3 explorer7 (NCT04083781) and explorer8 (NCT04082429) concizumab trials and the risk mitigations incorporated in the explorer clinical trials. Methods The explorer7 and explorer8 trials were initiated in late 2019 to evaluate the efficacy and safety of concizumab prophylaxis in HA/HB patients with/without inhibitors, respectively. Concizumab was administered subcutaneously with a 1.0 mg/kg loading dose (concizumab-naïve patients only) and a maintenance dose of 0.25 mg/kg daily from the second day onwards. Results In March 2020, explorer7 and explorer8 were paused due to the occurrence of two arterial and three venous thrombotic SAEs in three patients with HA or HB with inhibitors. All three patients had thrombotic risk factors present at baseline and had used concomitant hemostatic medication on the day of, and in two cases in the days up to, event onset. Two of the patients were among those with the highest concizumab exposure measured during phase 3. Laboratory parameters in all three patients were as expected. Based on these analyses, risk mitigation plans were developed, including guidelines for the concomitant use of hemostatic agents in the management of bleeding episodes while on concizumab prophylaxis and updates to the concizumab dosing regimen. Conclusion Novo Nordisk has assessed all available data and defined risk mitigation strategies and changes to the explorer trial protocols. Disclosures Seremetis: Novo Nordisk Ins: Current Employment, Current equity holder in private company. Cepo:Novo Nordisk: Current Employment. Skovgaard Rasmussen:Novo Nordisk: Current Employment. Høyer Rose:Novo Nordisk A/S: Current Employment, Divested equity in a private or publicly-traded company in the past 24 months. Tamer:Novo Nordisk: Current Employment, Current equity holder in private company, Divested equity in a private or publicly-traded company in the past 24 months. Porstmann:Novo Nordisk Health Care A/G: Current Employment. Haaning:Novo Nordisk: Current Employment, Current equity holder in publicly-traded company.

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Patient Reported Outcomes Among Systemic Mastocytosis (SM) Patients in Routine Clinical Practice: Results from the TouchStone Survey

Blood ◽

10.1182/blood-2020-137480 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 37-37

Author(s):

Ruben A. Mesa ◽

Erin M. Sullivan ◽

David Dubinsky ◽

Brittany Carroll ◽

Valerie M. Slee ◽

...

Keyword(s):

Mast Cell ◽

Research Funding ◽

Patient Reported Outcomes ◽

Publicly Traded ◽

Ability To Work ◽

The Past ◽

Stomach Pain ◽

Patient Reported ◽

Ed Visits ◽

Mean Time

Introduction: SM is a rare, clonal mast cell neoplasm characterized by uncontrolled proliferation and activation of mast cells driven by the KIT D816V mutation, which leads to severe and unpredictable symptoms. This study evaluated disease and healthcare system burden of SM in a real-world treatment setting in the US. Methods: In this cross-sectional study, SM patients recruited through the Mast Cell Connect Registry completed an online survey. The 100-item survey consists of symptom assessments using the ISM-SAF© and widely used patient-reported outcomes (PRO) measures including the Short Form (SF)-12, Work Productivity and Activity Impairment (WPAI), and questions regarding SM-related medication and physician and emergency department (ED) visits during the past year. Patients ≥18 years with a self-reported diagnosis were included after providing informed consent. Established PRO measures were scored using established scoring algorithms. Data from the first 30 patients enrolled were analyzed using descriptive statistics. Results: Thirty patients completed the survey: 87% female; mean age of 54 years; mean time since diagnosis of 8 years; mean time from symptom onset to diagnosis of 7 years; 80% reported indolent SM, 10% reported aggressive SM, 3% reported smoldering SM, and the remainder (7%) were uncertain of their type. Ninety percent reported ≥10 symptoms during the past year, the most bothersome being abdominal/stomach pain (17%), anaphylactic episodes (13%), diarrhea/loose stools (13%), and fatigue (10%). Most patients indicated they have moderate (43%) or severe (33%) disease. Symptom Burden and Quality of Life (QoL) Impact Mean ± SD mental and physical component summary scores from the SF-12 were 44 ± 1.8 and 43 ± 2.5, respectively, indicating below average health and mental well-being. The mean total symptom score (TSS) from the ISM-SAF was 50, with >28 indicating moderate-severe SM. Nearly all (27/30) patients reported that they strongly agreed (27%), agreed (40%) or somewhat agreed (23%) that SM had a negative impact on their QoL, and 50% (15/30) reported feeling a great deal (17%), quite a bit (10%), or somewhat (23%) depressed or discouraged due to their disease. Use of Healthcare Services & Medications Patients reported encounters with multiple physicians over the course of 1 year (Table). Most patients (90%) reported taking ≥2 over-the-counter (OTC) medications, and 40% of patients reported taking >3 prescription medications to manage SM. Twenty percent of survey respondents visited the ED due to anaphylaxis, with 50% of these patients requiring ED care for anaphylaxis on 3 different occasions. Fifty-seven percent (17/30) of patients reported managing at least 1 anaphylactic episode at home without visiting the ED, with 4 of these patients reporting ≥12 anaphylactic episodes within the past year. Work Impairment Limited activities due to pain attributed to SM were reported by 60% (18/30) of patients, and 56% (17/30) of patients indicated that pain interfered with their ability to work. 17% of respondents reported they were unable to work for pay, 46% of patients reported having to reduce work hours because of SM, and 20% of patients had filed for disability, all due to SM. Conclusions: Despite close management by healthcare providers, and taking prescription and OTC medications, early findings from the TouchStone survey show that the majority of SM patients continue to report significant burden of disease, including inadequate symptom control, negative effects on QoL, reduced ability to work, frequent physician visits to manage SM and multiple, potentially costly, ED visits. These findings suggest high unmet medical need underscoring the value of more effective therapeutic interventions. Disclosures Mesa: LaJolla Pharma: Consultancy; Novartis: Consultancy; Sierra Onc: Consultancy; Abbvie: Research Funding; Celgene: Research Funding; CTI: Research Funding; Genetech: Research Funding; Incyte: Research Funding; Promedior: Research Funding; Samus: Research Funding. Sullivan:Blueprint Medicines Corporation: Current Employment, Current equity holder in publicly-traded company. Dubinsky:Blueprint Medicines Corporation: Current Employment, Current equity holder in publicly-traded company. Carroll:Blueprint Medicines Corporation: Consultancy, Current equity holder in publicly-traded company. Mathias:Blueprint Medicines Corporation: Other: employed by Health Outcomes Solutions, which received funding Blueprint for providing assistance in developing the Touchstone survey. Castells:Annals of Allergy, Asthma & Immunology: Other: Editorial Board; UpToDate: Other: Author fee; Blueprint Medicines Corporation: Consultancy, Other: Clinical trials: Principle Investigator.

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Responsiveness of standard spine outcome tools: do they measure up?

Journal of Neurosurgery Spine ◽

10.3171/2019.12.spine191367 ◽

2020 ◽

Vol 33 (1) ◽

pp. 106-113

Author(s):

Carolyn E. Schwartz ◽

Roland B. Stark ◽

Phumeena Balasuberamaniam ◽

Mopina Shrikumar ◽

Abeer Wasim ◽

...

Keyword(s):

Random Effects ◽

Subjective Assessment ◽

Important Change ◽

Quality Data ◽

Random Effects Models ◽

Component Score ◽

Patient Reported ◽

Clinically Important Change ◽

Main Effects ◽

Spine Outcome

OBJECTIVEOver the past 2 decades, spine outcome research has become more standardized in response to recommendations from Deyo and others. By using the same generic and condition-specific patient-reported outcome (PRO) measures across studies, results are more easily compared. Given the challenges of maintaining high-quality data in clinical research studies, it would be important to evaluate the contribution of each PRO to confirm that it merits the respondent burden. This study aimed to examine the spine PROs’ association with clinically important change and relative responsiveness in explaining variance in patients’ global assessment of change (GAC).METHODSThis prospective longitudinal cohort study included adults recruited from 4 active spine surgery practices at a Toronto-based hospital. Patients were diagnosed with a degenerative lumbar spinal condition and underwent spinal decompression and/or fusion surgery. Participants completed the RAND-36 (to generate the physical component score [PCS] and mental component score [MCS]), Oswestry Disability Index (ODI), the numeric rating scale (NRS) for pain, Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference, and a GAC item. Random-effects models were used to investigate the sensitivity of PROs to the GAC and their responsiveness over time (i.e., PRO main effects and PRO-by-time interactions, respectively).RESULTSThe study sample included 168 patients (mean age 61 years, 50% female) with preoperative and up to 12 months of postoperative data. Random-effects models revealed significant main effects for all PROs. Significant time-by-PRO interactions were detected for the PCS, PROMIS, ODI, and NRS (p < 0.0005 in all cases), but not for the MCS. Further examination revealed different sensitivity of the PROs to the GAC at different times. The NRS, PROMIS, and PCS showed higher sensitivity early after surgery, and the PCS evinced a marked drop in sensitivity to the GAC at about 8 months postsurgery.CONCLUSIONSAll PROs currently included in the spine outcome core measures are associated with patients’ subjective assessment of a clinically important change, and all but the MCS scores are responsive to such change. Based on these findings, the core spine PROs could be reduced to include fewer estimates of pain. The authors suggest replacing the less responsive measures with tools that help to characterize factors that are driving the patients’ subjective assessment of change and that meaningfully address some of the higher levels in the hierarchy of quality-of-life outcomes.

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