scholarly journals Development of Patient-Reported Outcome Measures (Symptoms and Impacts) in Adults with Pyruvate Kinase Deficiency

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3447-3447
Author(s):  
Sam Salek ◽  
Audra N. Boscoe ◽  
Chris Evans ◽  
Shayna Egan ◽  
Ted Wells ◽  
...  
Keyword(s):  
Pyruvate Kinase ◽  
Research Funding ◽  
Patient Reported Outcome ◽  
Psychometric Validation ◽  
Specific Patient ◽  
Patient Reported ◽  
Item Wording ◽  
Eortc Qlq C30 ◽  
Eortc Qlq ◽  
Disease Specific

Introduction: Pyruvate kinase (PK) deficiency is a rare, congenital autosomal recessive hemolytic anemia managed with supportive treatments, including transfusion, splenectomy, and iron chelation. Disease-directed treatments, including a small molecule PK activator and gene therapy, are currently in development. No disease-specific patient-reported outcome (PRO) measures have been validated for use in this patient population. The objective of this initiative was to develop PRO measures for assessing symptoms and impacts of PK deficiency and compare them to existing, non-disease-specific measures previously recommended for use in this disease area. Methods: A targeted literature review was conducted to inform the development of a preliminary hypothesized conceptual framework to identify signs, symptoms, and impacts commonly experienced by patients with PK deficiency and to inform the direction and content of interviews with such patients. Concept elicitation interviews were conducted with 21 adults with PK deficiency from the US, Netherlands, and Germany. Draft items were then tested in cognitive interviews with 20 adults with PK deficiency to further establish content validity and revised based on the results. A comparison was conducted between concepts included in the newly developed PK deficiency disease-specific measures and the domain structure and item concepts included in the EORTC QLQ-C30 and SF-36v2 to evaluate the extent of differences and conceptual overlap with instruments that had previously been recommended in this population. Specific attributes compared included face validity (i.e., conceptual coverage and inclusion of proximal symptoms and/or impacts) and measurement characteristics (i.e., item wording, recall, and response options). Results: Two measures, the PK Deficiency Diary (PKDD), a 7-item measure of the core signs and symptoms of PK deficiency, and PK Deficiency Impact Assessment (PKDIA), a 14-item measure of the impacts of PK deficiency on patients' HRQoL, were developed. A comparison of the newly drafted measures to the EORTC QLQ-C30 and SF-36v2 demonstrated minimal similarities in concepts, domains, item wording, and recall period. Of the 7 concepts in the PKDD, only 3 were common to the EORTC QLQ-C30, 4 were common to the SF36v2, and 2 were related but did not match exactly (i.e., "bone pain" and "pain"). Of the 12 distinct concepts in the PKDIA, only 5 were common to the EORTC QLQ-C30, 2 were common to the SF-36v2, and 3 were related but did not match exactly (i.e., difficulty starting things, difficulty finishing things, and difficulty performing moderate physical activity). Conclusions: This research demonstrates that the EORTC-QLQ-C30 and SF-36v2 lack the appropriate conceptual relevance and coverage of disease-specific signs, symptoms, and impacts most relevant and burdensome to patients with PK deficiency. The newly developed PKDD and PKDIA may be useful tools in clinical trials in patients with PK deficiency. Psychometric validation of these measures is currently underway. Disclosures Salek: Pfizer: Honoraria, Speakers Bureau; Merck: Consultancy; Agios Pharmaceuticals, Inc.: Consultancy, Honoraria. Boscoe:Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Evans:Agios Pharmaceuticals, Inc.: Consultancy, Research Funding. Egan:Agios Pharmaceuticals, Inc.: Consultancy, Research Funding. Wells:Agios Pharmaceuticals, Inc.: Consultancy, Research Funding. Piantedosi:Agios Pharmaceuticals, Inc.: Employment. Grace:Agios Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding. Storm:Agios: Employment.

scholarly journals Not All Patients with Mild Phenotype of Gaucher Disease (GD) Need Disease Specific Treatment As Reflected By Patients Reported Outcomes Measures

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4712-4712
Author(s):  
Shoshana Revel-Vilk ◽  
Tama Dinur ◽  
Majdolen Istaiti ◽  
Dafna Frydman ◽  
Michal Becker-Cohen ◽  
...  
Keyword(s):  
Functional Status ◽  
Gaucher Disease ◽  
Research Funding ◽  
Financial Burden ◽  
Specific Therapy ◽  
Specific Patient ◽  
Mild Phenotype ◽  
Patient Reported ◽  
Disease Specific

The introduction of disease specific therapy for patients with type 1 Gaucher disease (GD) was a revolution in the management of patients, but not without significant cost to the patient and to society. The management of mildly effected patients is still debated, and reviews about GD as well as chapters in textbooks fail to emphasize the fact that some patients may remain untreated for many years without any GD-related complications. Patient reported outcome measures (PROMs) were developed as a way to ascertain patients' views of their symptoms, their functional status, and their health-related quality-of-life (HRQoL). In this study, we evaluated the responses to a GD -specific PROM of untreated patients with GD1 and compared them to patients on GD-specific therapy. Methods: A PROM survey was developed for GD including 15 questions; six Point Verbal Response Scale regarding the last month and nine Visual Analogue Scales (VAS) from 0-10 regarding the last week (Elstein D, et al. Molecular Genetics and Metabolism 2019;126:S52). The PROM survey was proven to be accurate in encompassing disease-specific patient concerns. A Hebrew translated version of the GD-PROM was sent via mobile phone survey to 400 adult patients with type 1 GD followed in our Gaucher Unit. Clinical data and treatment status were extracted from the clinical charts. T-test and Mann-Whitney U test were used to compare normally and non-normally distributed data in independent samples, respectively. IBM SPSS version 25 was used for analysis. Results were considered to be statistically significant when two-tailed P-values were ≤0.01. Results: A total of 181 patients responded (45% response rate) of whom 65 (36%) were followed for at least 5 years in our unit without receiving GD specific therapy, i.e. enzyme replacement therapy (ERT) and/or substrate reduction therapy (SRT). The median (range) age of patients, 49 (20-91) years, was not significantly different between treated and untreated patients. The percentage of patients with the N370S/N370S genotype was significantly higher in untreated patients [55/65 (85%)] compared to treated patients [67/116 (57%)]. Significantly more treated patients reported that GD had restricted their education/job (38, 34%) and fun activities (29,25%) compared to untreated patients, (4, 6.5%) and (2, 3%), respectively. Compared to untreated patients, treated patients were more worried to be an emotional burden on others [27 (23%) vs. 3 (5%)], of being financial burden on others [57 (50%) vs. 16 (25%)] and more concerned regarding the risk of bone disease [82 (74%) vs. 26 (40%)], and the risk of Parkinson disease [72 (64%) vs. 27 (42%)]. Treated patients had a significantly higher score on VAS for questions on swollen abdomen, fatigue, physical weakness, severity of bone pain and worry regarding the future over the past week compared to untreated patients (Table 1). Patients concern regarding the risk for cancer (32%) and VAS score for a question on depression were similar between groups. Conclusion:The GD-specific PROM survey shows that asymptomatic or mildly affected untreated patients with GD1 have good functional status and HRQoL, supporting our practice that not all patients with GD1 require disease-specific therapy. Still, we advise a periodic (annual or bi-annual) follow-up, preferably at a referral center. Inclusion of GD-specific PROMs in the periodic assessments is important for better understanding patients' perspectives. It is important to note that mildly affected and asymptomatic patients are mainly found among Ashkenazi Jews and from this aspect our cohort reflects patients' populations in Israel, USA, UK, etc. but less relevant to non-Jewish and particularly to Asian cohorts. With the expected increase in early diagnosis via parental and/or newborn screening the understanding that not all subjects diagnosed with GD needs disease-specific therapy is all the more important. Despite the expected differences between the more severely affected treated patients and the by definition milder untreated ones, still a high percentage of the treated patients show good HRQoL parameters, reflecting the overall success of ERT/SRT. Larger cohorts and further analysis will evaluate potential predictors for differences in PROMs within the treatment group. Disclosures Revel-Vilk: Sanofi: Honoraria, Other: Travel, Research Funding; Pfizer: Honoraria, Other: Travel, Research Funding; Takeda: Honoraria, Other: Travel, Research Funding; Prevail therapeutics: Honoraria, Other: Travel, Research Funding. Zimran:Prevail Therapeutics: Consultancy; TAKEDA: Honoraria; Centogene: Other: research grant; Targeted Cell Therapies: Consultancy; Pfize: Honoraria, Research Funding; Shire: Consultancy, Honoraria, Research Funding; Bio-events: Honoraria.

Prospective Validation of the Italian Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF: Italian) In 186 MPN Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5060-5060
Author(s):  
Robyn Scherber ◽  
Tiziano Barbui ◽  
Alessandro M. Vannucchi ◽  
Francesco Passamonti ◽  
Giovanni Barosi ◽  
...  
Keyword(s):  
Research Funding ◽  
Patient Reported Outcomes ◽  
Myeloproliferative Neoplasm ◽  
Office Visit ◽  
Symptom Assessment ◽  
Advisory Committees ◽  
Patient Reported ◽  
Eortc Qlq C30 ◽  
The Usa ◽  
Eortc Qlq

Abstract Abstract 5060 Background: The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) is a concise instrument of patient reported outcomes (PRO) designed to assess the unique spectrum of symptoms present in the majority of patients (Mesa et. al. Cancer 2007). We sought to validate the Italian Translation of the MPN-SAF which addresses 19 separate symptoms reported by MPN patients. Methods: Translation: We utilized the standard practice of PRO translation in which 3 independent translations are created by 3 independent translators fluent in both languages. A fourth translator then discussed the translations with the other translators and a consensus translation was obtained. Validation: Patients self completed the MPN-SAF: Italian at the time of a physician office visit and the Italian EORTC-QLQ-C30 (a widely used instrument of PRO for cancer patients) was co-administered for validation purposes. Results: Patients and Symptomatic Burden: 186 patients were prospectively enrolled (ET (N=88; 47%), PV (N=69; 37%) and MF (N=29; 16%)) a median of 6 years (range:0-29) from their diagnosis. Patients were of a median age (62; range 29–91 years) and gender (56% females) typical of the disease. 72% (N=135) had received some form of non-aspirin medical therapy for their disease, and 68% were on therapy at the time of completing the questionnaire. Patients frequently had a history of either thrombotic events (31%) and/or hemorrhagic events (13%). The MPN-SAF measured 19 items in the enrolled patients (data summarized in Table 1). Validation Analysis: EORTC-QLQ-C30: Consistent with our experience with the MPN-SAF:English, Pearson correlations between MPN-SAF:Italian individual symptom scores and the Italian EORTC-QLQ C30 showed excellent correlations with co-validation questions including fatigue, pain, insomnia, (all p<0.001). Excellent correlations were demonstrated between EORTC-QLQ-C30 subscales and corresponding MPN-SAF measurements. Comparison with MPN-SAF:English: Comparison with 102 patients prospectively completing the MPN-SAF: English (ET=20, PV=23, MF=59) in the USA indicated very strong correlations (when controlling for MPN subtype) in the prevalence of all 19 items assessed and only subtle differences in terms of symptomatic severity for fatigue, itching and insomnia. Conclusions: The MPN-SAF:Italian is an easy to administer, clear, 19-item inventory of patient-reported outcomes that is specific to MPNs. Additionally, the instrument is validated by 1) comparison to previously validated Italian instruments and 2) the correlation with the MPN-SAF:English. Utilization of the instrument in Italian MPN clinical trials will allow for useful comparison to patients completing the MPN-SAF in other countries and will serve as a valuable clinical marker of disease symptom severity. Disclosures: Vannucchi: Novartis: Membership on an entity's Board of Directors or advisory committees. Mesa:SBio: Research Funding; Novartis: Research Funding; Celgene: Research Funding; Incyte: Research Funding; Roche: Research Funding; eisai: Research Funding; telik: Research Funding.

scholarly journals Development and validation of Gaucher disease type 1 (GD1)-specific patient-reported outcome measures (PROMs) for clinical monitoring and for clinical trials

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Deborah Elstein ◽  
Nadia Belmatoug ◽  
Patrick Deegan ◽  
Özlem Göker-Alpan ◽  
Derralynn A. Hughes ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Patient Reported Outcome Measures ◽  
Patient Reported Outcome ◽  
Psychometric Validation ◽  
Specific Patient ◽  
Patient Reported ◽  
Test Retest Reliability ◽  
Development And Validation ◽  
The Impact

Abstract Background Disease-specific patient-reported outcome measures (PROMs) are fundamental to understanding the impact on, and expectations of, patients with genetic disorders, and can facilitate constructive and educated conversations about treatments and outcomes. However, generic PROMs may fail to capture disease-specific concerns. Here we report the development and validation of a Gaucher disease (GD)-specific PROM for patients with type 1 Gaucher disease (GD1) a lysosomal storage disorder characterized by hepatosplenomegaly, thrombocytopenia, anemia, bruising, bone disease, and fatigue. Results and discussion The questionnaire was initially developed with input from 85 patients or parents of patients with GD1 or GD3 in Israel. Owing to few participating patients with GD3, content validity was assessed for patients with GD1 only. Content validity of the revised questionnaire was assessed in 33 patients in the US, France, and Israel according to US Food and Drug Administration standards, with input from a panel of six GD experts and one patient advocate representative. Concept elicitation interviews explored patient experience of symptoms and treatments, and a cognitive debriefing exercise explored patients’ understanding and relevance of instructions, items, response scales, and recall period. Two versions of the questionnaire were subsequently developed: a 24-item version for routine monitoring in clinical practice (rmGD1-PROM), and a 17-item version for use in clinical trials (ctGD1-PROM). Psychometric validation of the ctGD1-PROM was assessed in 46 adult patients with GD1 and re-administered two weeks later to examine test–retest reliability. Findings from the psychometric validation study revealed excellent internal consistency and strong evidence of convergent validity of the ctGD1-PROM based on correlations with the 36-item Short Form Health Survey. Most items were found to show moderate, good, or excellent test–retest reliability. Conclusions Development of the ctGD1-PROM represents an important step forward for researchers measuring the impact of GD and its respective treatment.

Prospective Validation of the Swedish Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF: Swedish) In 114 MPN Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5053-5053
Author(s):  
Peter L. Johansson ◽  
Bjorn Andreasson ◽  
Robyn Scherber ◽  
Amylou Dueck ◽  
Jan Samuelsson ◽  
...  
Keyword(s):  
Research Funding ◽  
Patient Reported Outcomes ◽  
Myeloproliferative Neoplasm ◽  
Office Visit ◽  
Symptom Assessment ◽  
Early Satiety ◽  
Patient Reported ◽  
Eortc Qlq C30 ◽  
And Gender ◽  
Eortc Qlq

Abstract Abstract 5053 Background: The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) is a concise instrument of patient reported outcomes (PRO) designed to assess the unique spectrum of symptoms present in the majority of patients (Mesa et. al. Cancer 2007). We sought to validate the Swedish Translation of the MPN-SAF which addresses 19 separate symptoms reported by MPN patients. Methods: We utilized the standard practice of PRO translation in which 3 independent translations are created by 3 independent translators fluent in both languages. A fourth translator then discussed the translations with the other translators and a consensus translation was obtained. Patients self completed the MPN-SAF: Swedish at the time of a physician office visit and the Swedish EORTC-QLQ-C30 was co-administered for validation purposes. Results: Patients and Symptomatic Burden: 114 patients were prospectively enrolled (ET (N=53; 47%), PV (N=53; 47%) and MF (N=8; 6%)) a median of 6 years (range:0-42) from their diagnosis. Patients were of a median age (68; range 27–88 years) and gender (53% females) typical of the disease. 78% (N=88) had received some form of non-aspirin medical therapy for their disease, and 75% were on therapy at the time of completing the questionnaire. Patients frequently had a history of either thrombotic events (26%) and/or hemorrhagic events (10%). The MPN-SAF measured 19 items in the enrolled patients (data summarized in Table 1). Validation Analysis: EORTC-QLQ-C30 Consistent with our experience with the MPN-SAF:English Pearson correlations between MPN-SAF-Swedish individual symptom scores and the Swedish EORTC-QLQ C30 showed excellent correlations with co-validation questions including fatigue, pain, headache, insomnia, early satiety, and sad mood (all p<0.001). Correlations with EORTC-QLQ-C30 subscales demonstrated excellent correlations between MPN-SAF measurements and corresponding subscales. Comparison with Mpn-Saf:English: Comparison with 102 patients prospectively completing the MPN-SAF: English (ET=20, PV=N=23, MF=59) showed (when adjusting for MPN subtype) excellent correlation with all but 3 items in which the prevalence of the symptoms was similar but the severity less in the Swedish cohort (early satiety, headache and impaired quality of life). Additionally, the ranking of the prevalence of symptoms was very well correlated between both cohorts when controlling for disease type. Conclusions: The MPN-SAF: Swedish is an easy to administer, clear, 19 item inventory of patient reported outcomes that is specific to MPNs. Additionally, the instrument is validated by 1) comparison to previously validated Swedish Instruments and 2) the correlation with the MPN-SAF:English. Utilization of the instrument in Swedish MPN clinical trials will allow for useful comparison to patients completing the MPN-SAF in other countries. Disclosures: Samuelsson: Roche Sweden: Mesa: SBio: Research Funding; Novartis: Research Funding; Celgene: Research Funding; Incyte: Research Funding; Roche: Research Funding; eisai: Research Funding; telik: Research Funding.

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