Swedish translation and cultural adaptation of the scored Patient-Generated Subjective Global Assessment (PG-SGA©)-A validated tool for screening and assessing malnutrition in clinical practice and research.

INTRODUCTION: The scored Patient-Generated Subjective Global Assessment (PG-SGA©) is a validated tool for the screening, assessment and monitoring of malnutrition, and triaging of interventions. It contains a patient-generated component and a healthcare professional (HCP)-generated component. AIM: To translate the PG-SGA into Swedish, assess the linguistic and content validity of the Swedish version, and ensure conceptional, semantic and operational equivalence to the original English PG-SGA. METHODS: In line with the methodology used in previously translated and culturally adapted versions, the standardised 10-step process suggested by the International Society for Health Economics and Outcomes Research (ISPOR) was followed. In step 7, a cross-sectional study targeting patients n = 51 and HCPs n = 52 was performed at a university hospital in Sweden. Using separate questionnaires, patients assessed the patient component and HCPs, the professional component regarding perceived comprehensibility and difficulty (linguistic validity). The HCPs also assessed perceived relevance (content validity) of all items on the PG-SGA. Item indices for comprehensibility (I-CI), difficulty (I-DI) and content validity (I-CVI) were calculated and averaged into scale indices (S-CI, S-DI and S-CVI). Cut-off standards for item and scale indices were used as reference. RESULTS: The Swedish version of the PG-SGA rated excellent for comprehensibility (S-CI 0.96) and difficulty (S-DI 0.93) for the patient component. The professional component rated acceptable for comprehensibility (S-CI 0.89) and below acceptable for difficulty (S-DI 0.70), with the physical examination rated most difficult (I-DI 0.39 to 0.69). Content validity for the full Swedish PG-SGA was rated excellent (S-CVI 0.94). CONCLUSION: The patient component was considered clear and easy to complete. The full Swedish PG-SGA was considered relevant by HCPs for screening and assessment of malnutrition. Due to perceived difficulty with the physical examination, training of Swedish HCPs in using the PG-SGA is essential before implementing the professional component into clinical practice or research.

Treating moderate-to-severe menopausal vasomotor symptoms with fezolinetant: analysis of responders using pooled data from two phase 3 studies (SKYLIGHT 1 and 2).

OBJECTIVES: The aims of the study were to further characterize the efficacy of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) due to menopause using responder analysis and to investigate whether efficacy, not adjusted for placebo, resulted in clinically meaningful within-patient change. METHODS: This prespecified analysis used pooled data from two phase 3, randomized, double-blind, placebo-controlled studies (SKYLIGHT 1 and 2). Responders were those experiencing ≥50%, ≥75%, ≥90%, or 100% reduction in VMS frequency from baseline to weeks 4 and 12. Responder analysis was performed for patient-reported outcome (PRO) measures to evaluate participants achieving a clinically meaningful within-patient change (not placebo adjusted) at week 4 and 12 versus baseline. Single responders were based on outcomes of VMS frequency, Patient-Reported Outcomes Measurement Information System Sleep Disturbance-Short Form 8b Total Score, Menopause-Specific Quality of Life (MENQoL) Total Score, and MENQoL VMS Domain Score. Double and triple responder analyses combined VMS frequency plus one or more of the PRO. Patient Global Impression of Change VMS was deemed a suitable anchor measure for meaningful within-patient change in VMS frequency. RESULTS: A greater proportion of fezolinetant-treated versus placebo-treated participants had ≥50%, ≥75%, ≥90%, or 100% reduction in VMS frequency from baseline to weeks 4 and 12. A greater proportion of responders were observed in the fezolinetant groups versus placebo at week 12 in all four single responder analyses. In the double and triple responder analyses, odds ratios were supportive of a beneficial effect for both doses of fezolinetant versus placebo. CONCLUSIONS: Fezolinetant was associated with significantly higher within-patient clinically meaningful improvement in important PRO, including VMS frequency, PROMIS SD SF 8b Total Score, MENQoL Total Score, and MENQoL VMS Domain Score.

Fezolinetant treatment of moderate-to-severe vasomotor symptoms due to menopause: effect of intrinsic and extrinsic factors in two phase 3 studies (SKYLIGHT 1 and 2).

OBJECTIVE: This study aimed to assess the efficacy of the neurokinin 3 receptor antagonist, fezolinetant, according to several intrinsic (individual related) and extrinsic (external influence) factors that may influence the frequency and severity of moderate-to-severe vasomotor symptoms (VMS) using pooled 12-week data from SKYLIGHT 1 and 2. METHODS: SKYLIGHT 1 and 2 were two phase 3, randomized, double-blind studies conducted from July 2019 to August 2021 (SKYLIGHT 1) or April 2021 (SKYLIGHT 2). Participants were initially randomized to receive daily doses of placebo, fezolinetant 30 mg, or fezolinetant 45 mg. After 12 weeks, placebo participants were rerandomized to receive fezolinetant 30 mg or 45 mg, whereas those receiving fezolinetant continued on the same dose. Change in VMS frequency from baseline to week 12 was used to assess efficacy according to several intrinsic and extrinsic factors. Overall efficacy and safety were also investigated. RESULTS: Overall, 1,022 individuals were included. Fezolinetant was efficacious in reducing VMS frequency across all intrinsic and extrinsic factors. Efficacy was most notable for participants who self-identify as Black (least squares mean difference for fezolinetant 45 mg versus placebo, -3.67; 95% CI, -5.32 to -2.01), current smokers (-3.48; -5.19 to -1.77), and current alcohol users (-3.48; -4.42 to -2.54). Overall efficacy was -2.51 (95% CI, -3.20 to -1.82) for fezolinetant 45 mg versus placebo. Similar findings were observed for the fezolinetant 30 mg dose. Comparable incidences of treatment-emergent adverse events were observed for placebo (132 of 342 individuals [38.6%]), fezolinetant 30 mg (132 of 340 individuals [38.8%]), and fezolinetant 45 mg (135 of 340 individuals [39.7%]). CONCLUSIONS: None of the intrinsic and extrinsic factors analyzed substantially reduced the efficacy response to fezolinetant in SKYLIGHT 1 and 2. These data provide additional confidence for using fezolinetant in a diverse population of individuals with VMS.

Fezolinetant impact on health-related quality of life for vasomotor symptoms due to the menopause: Pooled data from SKYLIGHT 1 and SKYLIGHT 2 randomised controlled trials.

OBJECTIVE: To assess the effect of fezolinetant treatment on health-related quality of life using pooled data from SKYLIGHT 1 and 2 studies. DESIGN: Prespecified pooled analysis. SETTING: USA, Canada, Europe; 2019-2021. POPULATION: 1022 women aged ≥40 to ≤65 years with moderate-to-severe vasomotor symptoms (VMS; minimum average seven hot flushes/day), seeking treatment for VMS. METHODS: Women were randomised to 12-week double-blind treatment with once-daily placebo or fezolinetant 30 or 45 mg. Completers entered a 40-week, active extension (those receiving fezolinetant continued that dose; those receiving placebo re-randomised to fezolinetant received 30 or 45 mg). MAIN OUTCOME MEASURES: Mean changes from baseline to weeks 4 and 12 on Menopause-Specific Quality of Life (MENQoL) total and domain scores, Work Productivity and Activity Impairment questionnaire specific to VMS (WPAI-VMS) domain scores, Patient Global Impression of Change in VMS (PGI-C VMS); percentages achieving PGI-C VMS of 'much better' (PGI-C VMS responders). Mean reduction was estimated using mixed model repeated measures analysis of covariance. RESULTS: Fezolinetant 45 mg mean reduction over placebo in MENQoL total score was -0.57 (95% confidence interval [CI] -0.75 to -0.39) at week 4 and -0.47 (95% CI -0.66 to -0.28) at week 12. Reductions were similar for 30 mg. MENQoL domain scores were also reduced and WPAI-VMS scores improved. Twice as many women receiving fezolinetant reported VMS were 'much better' than placebo based on PGI-C VMS assessment. CONCLUSIONS: Fezolinetant treatment was associated with improvement in overall QoL, measured by MENQoL, and work productivity, measured by WPAI-VMS. A high proportion receiving fezolinetant felt VMS were 'much better' based on PGI-C VMS responder analysis.

Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study.

BACKGROUND: Neurokinin 3 receptor antagonists are potential non-hormonal therapies for the treatment of vasomotor symptoms in menopausal women as options are scarce for those who cannot or do not want to take hormone therapy. Fezolinetant is one of the first non-hormonal neurokinin 3 receptor antagonists in development for the treatment of vasomotor symptoms due to menopause. This study investigated the safety and efficacy of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms associated with menopause. METHODS: SKYLIGHT 1 is a randomised, double-blind, placebo-controlled, 12-week, phase 3 trial with a 40-week active treatment extension. This trial was done at 97 facilities across the USA, Canada, Czech Republic, Hungary, Poland, Spain, and the UK. Women aged 40-65 years with an average of seven or more moderate-to-severe hot flashes per day were randomly assigned (1:1:1) to once-daily exact-matched placebo, fezolinetant 30 mg, or fezolinetant 45 mg. Randomisation was done using a web-based interactive response system and investigators, project team members, clinical staff, and participants were masked to treatment assignment. Coprimary endpoints were mean change in frequency and severity of vasomotor symptoms from baseline to weeks 4 and 12. The efficacy and safety analyses comprised all randomly assigned participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT04003155) and is completed. FINDINGS: Between July 11, 2019, and Aug 11, 2021, 2205 women were recruited of whom 175 were assigned to placebo, 176 to fezolinetant 30 mg, and 176 to fezolinetant 45 mg (175 in the placebo group, 174 in the fezolinetant 30 mg group, and 173 in the fezolinetant 45 mg received at least one dose [safety analysis set]). One participant randomly assigned to fezolinetant 45 mg received fezolinetant 30 mg in error, so the efficacy analysis set (full analysis set) consisted of 173 in the fezolinetant 30 mg group and 174 in the fezolinetant 45 mg group. 23 participants in the placebo group, 31 in the fezolinetant 30 mg group, and 13 in the fezolinetant 45 mg group discontinued treatment before week 12, mostly due to adverse events or participant withdrawal. Compared with placebo, fezolinetant 30 mg and fezolinetant 45 mg significantly reduced the frequency of vasomotor symptoms at week 4 (difference in change in least squares mean -1·87 [SE 0·42; p<0·001], -2·07 [SE 0·42; p<0·001]) and week 12 (-2·39 [SE 0·44; p<0·001], -2·55 [SE 0·43; p<0·001]). Compared with placebo, fezolinetant 30 mg and 45 mg significantly reduced the severity of vasomotor symptoms at week 4 (-0·15 [0·06; p=0·012], -0·19 [0·06; p=0·002]) and week 12 (-0·24 [0·08; p=0·002], -0·20 [0·08; p=0·007]). Improvements in frequency and severity of vasomotor symptoms were observed after 1 week and maintained over 52 weeks. During the first 12 weeks, treatment-emergent adverse events occurred in 65 (37%) of 174 women in the fezolinetant 30 mg group, 75 (43%) of 173 in the fezolinetant 45 mg group, and 78 (45%) of 175 in the placebo group. The incidence of liver enzyme elevations was low (placebo n=1; fezolinetant 30 mg n=2; fezolinetant 45 mg n=0) and these events were generally asymptomatic, transient, and resolved while on treatment or after treatment discontinuation. INTERPRETATION: Data support the clinical use of fezolinetant as a non-hormonal treatment for vasomotor symptoms associated with menopause. The study was placebo-controlled for 12 weeks followed by a 40-week blinded extension to assess the maintenance of effect. Furthermore, the population studied was diverse and representative of the potential target population for fezolinetant therapy. Further characterisation of the benefit of fezolinetant on quality of life, including on symptoms of mood and sexual wellbeing, merits investigation. FUNDING: Astellas Pharma.

Safety of Fezolinetant for Vasomotor Symptoms Associated With Menopause: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the safety, tolerability, and effect of fezolinetant on endometrial health over 52 weeks. METHODS: We conducted a phase 3, randomized, double-blind, 52-week safety study (SKYLIGHT 4 [Study to Find Out How Safe Long-term Treatment With Fezolinetant is in Women With Hot Flashes Going Through Menopause]) of placebo, fezolinetant 30 mg, and fezolinetant 45 mg once daily (1:1:1). Participants were postmenopausal and seeking treatment for vasomotor symptoms associated with menopause. Primary endpoints were treatment-emergent adverse events, percentage of participants with endometrial hyperplasia, and percentage with endometrial malignancy. Endometrial hyperplasia or malignancy was evaluated according to U.S. Food and Drug Administration guidance (point estimate of 1% or less with an upper bound of one-sided 95% CI of 4% or less). Secondary endpoints included change in bone mineral density (BMD) and trabecular bone score. A sample size of 1,740 was calculated to enable observation of one or more events (≈80% probability for events with background rate of less than 1%). RESULTS: A total of 1,830 participants were randomized and took one or more medication dose (July 2019-January 2022). Treatment-emergent adverse events occurred in 64.1% (391/610) of the placebo group, 67.9% (415/611) of the fezolinetant 30-mg group, and 63.9% (389/609) of the fezolinetant 45-mg group. Treatment-emergent adverse events leading to discontinuation were similar across groups (placebo, 26/610 [4.3%]; fezolinetant 30 mg, 34/611 [5.6%]; fezolinetant 45 mg, 28/609 [4.6%]). Endometrial safety was assessed in 599 participants. In the fezolinetant 45-mg group, 1 of 203 participants had endometrial hyperplasia (0.5%; upper limit of one-sided 95% CI 2.3%); there were no cases in the placebo (0/186) or fezolinetant 30 mg (0/210) group. Endometrial malignancy occurred in 1 of 210 in the fezolinetant 30-mg group (0.5%; 95% CI 2.2%) with no cases in the other groups. Liver enzyme elevations more than three times the upper limit of normal occurred in 6 of 583 placebo, 8 of 590 fezolinetant 30 mg, and 12 of 589 fezolinetant 45 mg participants; no Hy's law cases were reported (ie, no severe drug-induced liver injury with alanine aminotransferase or aspartate aminotransferase more than three times the upper limit of normal and total bilirubin more than two times the upper limit of normal, with no elevation of alkaline phosphatase and no other reason to explain the combination). Changes in BMD and trabecular bone score were similar across groups. CONCLUSION: Results from SKYLIGHT 4 confirm the 52-week safety and tolerability of fezolinetant and support its continued development. FUNDING SOURCE: Astellas Pharma Inc. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT04003389.

Translation and cultural adaptation of the scored Patient-Generated Subjective Global Assessment (PG-SGA©).

BACKGROUND AND AIM: The Patient-Generated Subjective Global Assessment (PG-SGA©) is a globally used malnutrition screening, assessment, triage and monitoring tool. The aim of this study was to perform a linguistic and content validation of the translated and culturally adapted version of the PG-SGA for the Danish setting. METHOD: The study was conducted according to the International Society of Pharmaeconomics and Outcomes Research (ISPOR) Principles of Good Practice for the Translational and Cultural Adaptation Process for Patient-Reported Outcomes Measures. Cancer patients (n = 121) and healthcare professionals (HCPs, n = 80) participated in the cognitive debriefing. A questionnaire was used in the cognitive debriefing in which comprehensibility, difficulty, and content validity (relevance) were quantified by a 4-point scale. Item and scale indices were calculated using the average item ratings divided by the number of respondents for content validity (Item-CVI, Scale-CVI), comprehensibility (Item-CI, Scale-CI) and difficulty (Item-DI, Scale-DI). As pre-defined, item indices <0.78 required further analysis of the item, and scale indices ≥0.90 were defined as excellent and 0.80-0.89 as acceptable. RESULTS: The patient component of the PG-SGA was rated as excellent content validity (Scale-CVI = 0.95) by HCPs and easy to comprehend (Scale-CI = 0.97) and use (Scale-DI = 0.92) by patients. The professional component of the PG-SGA was rated as acceptable content validity (Scale-CVI = 0.80), but below acceptable for comprehension (Scale-CI = 0.71) and difficulty (Scale-DI = 0.69). The physical exam was rated the least comprehensible Item-CI = 0.51-0.70) and most difficult (Item-DI = 0.33-0.063). CONCLUSION: The PG-SGA was successfully translated and culturally adapted to the Danish setting. Patients found it easy to understand and to complete. Except for the physical exam, HCPs rated the PG-SGA as relevant, comprehensive, and easy to use. Training of HCPs is recommended before implementing the tool into clinical practise.

Phase I/II study to assess the clinical pharmacology and safety of single ascending and multiple subcutaneous doses of PF-06881894 in women with non-distantly metastatic breast cancer.

PURPOSE: To evaluate the pharmacodynamics (PD), pharmacokinetics (PK), and safety of single and multiple doses of PF-06881894 (pegfilgrastim-apgf; Nyvepria™), a biosimilar to reference pegfilgrastim (Neulasta®), in women with non-distantly metastatic breast cancer. METHODS: In Phase I (Cycle 0) of this Phase I/II study, the PD response (absolute neutrophil count [ANC]; CD34 + count), PK profile, and safety of a single 3- or 6-mg subcutaneous dose of PF-06881894 were assessed in chemotherapy-naïve patients before definitive breast surgery. In Phase II (Cycles 1-4), the PD response (duration of severe neutropenia [DSN, Cycle 1], ANC [Cycles 1 and 4]) and PK profile (Cycles 1 and 4) of single and multiple 6-mg doses of PF-06881894 concomitant with chemotherapy and after definitive breast surgery were assessed. RESULTS: Twenty-five patients (mean age 59 years) were enrolled (Cycle 0, n = 12; Cycles 1-4, n = 13). In Cycle 0, PD responses and PK values were lower with 3-mg versus 6-mg PF-06881894. In Cycles 1 and 4, mean DSN was 0.667 days after single or multiple 6-mg doses of PF-06881894, respectively. In Cycle 4 versus Cycle 1, PD responses were more robust; PK values (mean area under the curve, maximum concentration) were lower; and clearance values were higher. The safety profile of PF-06881894 was similar to that for reference pegfilgrastim. CONCLUSION: PF-06881894 as a single 3- or 6-mg dose prior to definitive surgery, or multiple 6-mg/cycle doses postoperatively, with/without myelosuppressive chemotherapy, was consistent with the clinical pharmacology and safety profile of reference pegfilgrastim. TRIAL REGISTRATION: October 2017. ClinicalTrials.gov Identifier: NCT02650193. EudraCT Number: 2015-002057-35.

Greek translation and cultural adaptation of the scored patient-generated subjective global assessment: A nutritional assessment tool suitable for cancer patients.

BACKGROUND AND AIMS: Patients with cancer frequently present with disease-related malnutrition and functional decline. The scored Patient-Generated Subjective Global Assessment (PG-SGA©) is a malnutrition screening and assessment tool commonly used in patients with cancer. The aim of the current study was to translate and culturally adapt the original English PG-SGA for the Greek setting, including assessment of comprehensibility, difficulty and content validity in patients and healthcare professionals. METHODS: Our study was conducted according to the ten steps of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Principles of Good Practice for Translation and Cultural Adaptation. Comprehensibility and difficulty of the Greek translation were assessed in 100 patients and 100 healthcare professionals (HCPs) from Greece. Content validity of the translation was assessed among HCPs. Item and scale indices were calculated for comprehensibility (I-CI; S-CI), difficulty (I-DI; S-DI), and content validity (I-CVI; S-CVI). RESULTS: Patient perceived comprehensibility and difficulty of the PG-SGA were considered to be excellent (S-CI = 0.97, S-DI = 0.97). HCPs perceived content validity for the patient component was also excellent (S-CVI = 0.95). The perceived content validity, comprehensibility and difficulty for the professional component of the PG-SGA, as perceived by the HCPs, was excellent (S-CVI = 0.94, S-CI = 0.94, S-DI = 0.90), with the physical exam being perceived as most difficult (I-DI = 0.78-0.92). CONCLUSIONS: Our study resulted in the successful translation and cross-cultural adaptation of the original English PG-SGA for the Greek setting. The Greek language version of the PG-SGA is characterized by high comprehensibility, low difficulty, and is considered relevant for use in Greece.

A Japanese translation, cultural adaptation, and linguistic and content validity confirmation of the Scored Patient-Generated Subjective Global Assessment.

PURPOSE: The Scored Patient-Generated Subjective Global Assessment (PG-SGA©) is a globally recognized and used nutritional screening, assessment, monitoring, and triaging tool. The aim of this study was to translate and culturally adapt the original English PG-SGA for the Japanese speaking populations and to assess its linguistic validity (i.e., comprehensibility, difficulty) and content validity, as perceived by Japanese patients and healthcare professionals. METHODS: In accordance with methodology used in previous Dutch, Thai, German, and Norwegian PG-SGA studies, we followed the ten steps of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Principles of Good Practice for Translation and Cultural Adaptation for Patient-Reported Outcome Measures. The study enrolled 50 patients and 50 healthcare professionals (HCPs) to evaluate the comprehensibility and difficulty of the translated and culturally adapted PG-SGA. The HCPs also evaluated the content validity of the translation. We evaluated each item and quantified scale indices for content validity (item content validity index (I-CVI), scale content validity index (S-CVI)), comprehensibility (item comprehensibility index (I-CI), scale comprehensibility index (S-CI)), and difficulty (item difficulty index (I-DI), scale difficulty index (S-DI)). RESULTS: Patients evaluated the comprehensibility and difficulty of the patient component as excellent (S-CI = 0.97, S-DI = 0.96). The professionals rated the Japanese version of both components of the PG-SGA as very relevant (S-CVI = 0.94). The professionals evaluated the comprehensibility of the professional component as being acceptable (S-CI = 0.88) but difficult (S-DI = 0.69), based predominantly on items related to physical examination (I-DI = 0.33-0.67). CONCLUSION: The PG-SGA was systematically translated and culturally adapted for the Japanese setting according to the ISPOR process. The Japanese version of the PG-SGA was perceived as comprehensive, easy to use, and relevant. Perceived difficulty in professional components, specifically in the context of metabolic demand and physical examination, will require appropriate training for professionals in order to optimize implementation.

Linguistic and content validation of the translated and culturally adapted PG-SGA, as perceived by Norwegian cancer patients and healthcare professionals.

BACKGROUND & AIMS: The Scored Patient-Generated Subjective Global Assessment (PG-SGA©) is a validated nutritional screening, assessment, monitoring, and triage tool. When translated to other languages, the questions and answering items need to be conceptually, semantically, and operationally equivalent to the original tool. In this study, we aimed to assess linguistic and content validity of the PG-SGA translated and culturally adapted for the Norwegian setting, as perceived by Norwegian cancer patients and healthcare professionals (HCPs). METHODS: We have translated and culturally adapted the original PG-SGA for the Norwegian setting, in concordance with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Cancer patients and HCPs, including nurses, dietitians and physicians, were invited to participate. Comprehensibility and difficulty were assessed by patients for the patient component (PG-SGA Short Form), and by HCPs for the professional component. Content validity was assessed for the full PG-SGA by HCPs only. The data were collected by a questionnaire and evaluations were operationalized by a 4-point scale. Item and scale indices were calculated for comprehensibility (Item CI, Scale CI), difficulty (Item DI, Scale DI) and content validity (Item CVI, Scale CVI). RESULTS: Fifty-one cancer patients and 92 HCPs participated in the study. The patients perceived comprehensibility and difficulty of the Norwegian PG-SGA Short Form as excellent (Scale CI = 0.99 and DI = 0.97). However, HCPs perceived comprehensibility and difficulty of the professional component as below acceptable (Scale CI = 0.78 and DI = 0.66), and the physical exam was being rated as the most difficult part (Item DI 0.26 to 0.65). Content validity for the full Norwegian PG-SGA was considered excellent (Scale CVI = 0.99) by the HCPs. CONCLUSION: The patient component of PG-SGA was considered clear and easy to complete, and the full Norwegian PG-SGA was considered as relevant by HCPs. In the final Norwegian PG-SGA, changes have been made to improve comprehensibility of the professional component. To improve perceived difficulty of completing the professional component, training of professionals is indicated.

Self-Completion of the Patient-Generated Subjective Global Assessment Short Form Is Feasible and Is Associated With Increased Awareness on Malnutrition Risk in Patients With Head and Neck Cancer.

BACKGROUND: We aimed to assess feasibility of self-completion of the Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF) by head and neck cancer patients, and to assess self-reported increased awareness regarding malnutrition risk after self-completion. METHODS: Participants were randomized to complete the PG-SGA SF by paper or app. Feasibility was assessed by time needed to complete the PG-SGA SF, perceived difficulty, and help needed during completion. Participants were asked if they knew what malnutrition was (yes/no) and if they could define "malnutrition." They were also asked 9 questions on whether they perceived increased awareness of malnutrition risk after having completed the PG-SGA SF and 2 on their intention to change lifestyle habits. RESULTS: Of all participants (n = 59; 65.9 ± 12.6 years; 73% male), 55% completed the PG-SGA SF paper version and 46% the Pt-Global app. Median time needed for self-completion of the PG-SGA SF was 2 minutes 41 seconds (interquartile range: 1 minute 49 seconds-3 minutes 50 seconds). Forty-eight percent needed help with completion, indicating acceptable feasibility. Participants who completed the Pt-Global app needed help significantly more often (66%; 21/32) than those who completed the PG-SGA SF paper version (26%; 7/27) (P = 0.005). All difficulty scores were excellent. For 7/9 questions on malnutrition risk awareness, >50% of the participants answered positively. CONCLUSION: The results of this study show that self-completion of the PG-SGA SF by head and neck cancer patients is feasible and that awareness regarding malnutrition risk may increase after completing the PG-SGA SF.

Prevalence of Malnutrition or Risk in Residents in Long Term Care: Comparison of Four Tools.

The ideal tool for determination of malnutrition risk or malnutrition in long term care (LTC) is elusive. This study compares prevalence, association with resident risk factors and sensitivity (SE) and specificity (SP) of malnutrition or risk categorization in 638 residents from 32 LTC homes in Canada using four tools: the Mini-Nutritional Assessment Short Form (MNA-SF); Patient-Generated Subjective Global Assessment (PG-SGA) Global Category Rating and the Pt-Global webtool; and the interRAI Long Term Care Facility undernutrition trigger. Prevalence was most common with MNA-SF (53.7%) and lowest with InterRAI (28.9%), while the PG-SGA Global Category Rating (44%) was higher than the Pt-Global webtool (33.4%). Tools were consistently associated with resident covariates with few exceptions. The PG-SGA Global Category Rating demonstrated the best sensitivity and specificity when compared to all other tools. Further work to determine the predictive validity of this tool in LTC residents is required.

PF-06881893 (Nivestym™), a Filgrastim Biosimilar, Versus US-Licensed Filgrastim Reference Product (US-Neupogen®): Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Safety of Single or Multiple Subcutaneous Doses in Healthy Volunteers.

BACKGROUND: Three comparative clinical studies assessed the pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity and safety of PF-06881893 (filgrastim-aafi; Nivestym™), a filgrastim biosimilar, versus US-licensed reference product (filgrastim; US-Neupogen®) in healthy volunteers (HVs). METHODS: Two separate open-label, crossover-design PK/PD studies were conducted: a single-dose study (n = 24) and a multiple-dose study (n = 60). In each study, HVs were randomized to Nivestym followed by US-Neupogen, or vice versa. Study drug (5 µg/kg) was administered subcutaneously as a single injection or as five consecutive daily injections. Primary PK and PD endpoints were area under the filgrastim serum concentration-time curve, maximum observed concentration, area under the effect curve (AUEC) for absolute neutrophil count (ANC), maximum observed ANC, AUEC for cluster of differentiation (CD)-34+ count, and maximum observed CD34+ count. In an open-label, parallel-design, non-inferiority, comparative immunogenicity study, HVs were randomized (n = 128/treatment) to Nivestym or US-Neupogen. The primary endpoint was the proportion of subjects with a negative baseline antidrug antibody (ADA) test result and one or more confirmed post-dose positive ADA result. RESULTS: Overall demographics were as follows: female (n = 162/340); White (n = 274/340), Black (n = 58/340), and other (n = 8/340); age (18-65 years); and weight (50.8-96.5 kg). All primary PK and PD endpoints met the pre-specified criteria for PK and PD equivalence. The primary endpoint in the comparative immunogenicity study met pre-specified criteria for non-inferiority. CONCLUSIONS: Nivestym demonstrated PK and PD equivalence in single and multiple subcutaneous-dose settings and non-inferiority for immunogenicity to US-Neupogen, with a comparable safety profile, supporting the demonstration of biosimilarity. TRIAL REGISTRATION: ClinicalTrials.gov C1121002 (NCT02766647); C1121003 (NCT02766634); C1121012 (NCT02923791).

Tri-country translation, cultural adaptation, and validity confirmation of the Scored Patient-Generated Subjective Global Assessment.

PURPOSE: The Scored Patient-Generated Subjective Global Assessment (PG-SGA) is the only malnutrition (risk) assessment tool that combines patient-generated measures with professional-generated (medical) factors. We aimed to apply international standards to produce a high quality, validated, translation and cultural adaptation of the original PG-SGA for the Austrian, German, and Swiss setting. METHODS: Analogue to methodology used for the Dutch, Portuguese, and Thai versions of PG-SGA, the ten steps of the International Society for Pharmacoeconomics and Outcomes Research's principles of good practice for translation and cultural adaptation were followed. Comprehensibility and difficulty of the translation were assessed in 103 patients and 104 healthcare professionals recruited from all three German-speaking countries. Content validity of the translation was assessed among healthcare professionals (HCP). Item and scale indices were calculated for content validity (I-CVI; S-CVI), comprehensibility (I-CI; S-CI), and difficulty (I-DI; S-DI). RESULTS: Patients' perceived comprehensibility and difficulty of the PG-SGA fell within the range considered to be excellent (S-CI = 0.90, S-DI = 0.90), HCP-perceived content validity (S-CVI = 0.90) was also excellent, while HCP-perceived comprehensibility fell within the high range of acceptable (S-CI = 0.87). The professional component of the PG-SGA was perceived as below acceptable (S-DI = 0.72) with the physical exam being rated the most difficult (I-DI=0.29-0.75). CONCLUSIONS: The systematic approach resulted in a high-quality validation of the German language version of the PG-SGA, that is internationally comparable, comprehensible, easy to complete, and considered relevant for use in Austria, Germany and Switzerland.

Translation and Cultural Adaptation of the Scored Patient-Generated Subjective Global Assessment: An Interdisciplinary Nutritional Instrument Appropriate for Dutch Cancer Patients.

BACKGROUND: Assessment of malnutrition is important in cancer patients. The Scored Patient-Generated Subjective Global Assessment (PG-SGA), an instrument that enables interdisciplinary assessment of malnutrition and its risk factors, was not available in Dutch. OBJECTIVE: Translation and cultural adaption of the original English PG-SGA to the Dutch setting. METHODS: The PG-SGA was translated and culturally adapted, following the International Society for Pharmacoeconomics and Outcomes Research principles. Perceived content validity, comprehensibility, and difficulty were explored among a multidisciplinary sample of healthcare professionals and their cancer patients. Content validity, comprehensibility, and difficulty were operationalized by calculating item and scale indices. On scale level, indices of 0.80 to 0.90 were considered acceptable, and indices of 0.90 or greater were considered excellent. RESULTS: Consensus was reached on 91 and 8 differences in the forward and back translations, respectively. Scale Content Validity Index was 0.89. Scale Comprehensibility Index and Scale Difficulty Index of the patient-generated component of the PG-SGA were 0.99 and 0.96, respectively. Scale Comprehensibility Index and Scale Difficulty Index of the professional component were 0.81 and 0.55, respectively. CONCLUSIONS: Translation and cultural adaptation of the PG-SGA according to the International Society for Pharmacoeconomics and Outcomes Research principles resulted in a Dutch version that maintained the purpose, meaning, and format and have acceptable content validity. Now a Dutch version of the PG-SGA is available that is considered comprehensible and easy by patients, and comprehensible and relevant by professionals. However, the professional component was considered difficult by the PG-SGA-naive professionals, which indicates a need for training. IMPLICATIONS FOR PRACTICE: A similar systematic approach for future translations of the PG-SGA is recommended, to safeguard cultural equivalence.

Assessing nutritional status in cancer: role of the Patient-Generated Subjective Global Assessment.

PURPOSE OF REVIEW: The Scored Patient-Generated Subjective Global Assessment (PG-SGA) is used internationally as the reference method for proactive risk assessment (screening), assessment, monitoring and triaging for interventions in patients with cancer. This review aims to explain the rationale behind and data supporting the PG-SGA, and to provide an overview of recent developments in the utilization of the PG-SGA and the PG-SGA Short Form. RECENT FINDINGS: The PG-SGA was designed in the context of a paradigm known as 'anabolic competence'. Uniquely, the PG-SGA evaluates the patient's status as a dynamic rather than static process. The PG-SGA has received new attention, particularly as a screening instrument for nutritional risk or deficit, identifying treatable impediments and guiding patients and professionals in triaging for interdisciplinary interventions. The international use of the PG-SGA indicates a critical need for high-quality and linguistically validated translations of the PG-SGA. SUMMARY: As a 4-in-1 instrument, the PG-SGA can streamline clinic work flow and improve the quality of interaction between the clinician and the patient. The availability of multiple high-quality language versions of the PG-SGA enables the inclusion of the PG-SGA in international multicenter studies, facilitating meta-analysis and benchmarking across countries.

Content validity across methods of malnutrition assessment in patients with cancer is limited.

OBJECTIVE: To identify malnutrition assessment methods in cancer patients and assess their content validity based on internationally accepted definitions for malnutrition. STUDY DESIGN AND SETTING: Systematic review of studies in cancer patients that operationalized malnutrition as a variable, published since 1998. Eleven key concepts, within the three domains reflected by the malnutrition definitions acknowledged by European Society for Clinical Nutrition and Metabolism (ESPEN) and the American Society for Parenteral and Enteral Nutrition (ASPEN): A: nutrient balance; B: changes in body shape, body area and body composition; and C: function, were used to classify content validity of methods to assess malnutrition. Content validity indices (M-CVIA-C) were calculated per assessment method. Acceptable content validity was defined as M-CVIA-C ≥ 0.80. RESULTS: Thirty-seven assessment methods were identified in the 160 included articles. Mini Nutritional Assessment (M-CVIA-C = 0.72), Scored Patient-Generated Subjective Global Assessment (M-CVIA-C = 0.61), and Subjective Global Assessment (M-CVIA-C = 0.53) scored highest M-CVIA-C. CONCLUSION: A large number of malnutrition assessment methods are used in cancer research. Content validity of these methods varies widely. None of these assessment methods has acceptable content validity, when compared against a construct based on ESPEN and ASPEN definitions of malnutrition.

Infusion-related reactions with pegloticase, a recombinant uricase for the treatment of chronic gout refractory to conventional therapy.

BACKGROUND: In clinical trials of pegloticase, a PEGylated uricase developed for treatment of gout refractory to conventional therapy, infusion-related reactions (IRs) were the second most frequent adverse event reported. OBJECTIVE: The objective of this study was to provide a detailed account of IRs with pegloticase therapy. METHODS: Data from 2 replicate, 6-month randomized trials and an open-label extension study were pooled. Infusions of pegloticase (8 mg) were administered biweekly or monthly; all patients received prophylaxis (antihistamine, acetaminophen, and corticosteroid) and were tested for urate levels prior to each infusion. An IR was defined by protocol as any otherwise unexplained adverse event or cluster of temporally related events occurring during or within 2 hours of infusion. RESULTS: Infusion-related reactions occurred in 94 (45%) of 208 patients receiving pegloticase; 10 patients reported IRs at first infusion and 84 during subsequent infusions. Chest discomfort (15%), flushing (12%), and dyspnea (11%) were the most common symptoms. Most IRs were rated mild or moderate; 7% were rated severe. All IRs resolved with slowing, interrupting, or stopping the infusion. No patient required blood pressure or ventilatory support. Infusion-related reactions were associated with loss of pegloticase urate-lowering efficacy: 91% of all IRs occurred in patients with preinfusion serum uric acid concentrations (sUA) greater than 6 mg/dL. For patients sustaining preinfusion sUA of less than 6 mg/dL, IRs occurred in fewer than 1 per 100 infusions. CONCLUSIONS: Phase 3 trial data combined with post hoc analyses demonstrated that knowledge of sUA preceding each pegloticase infusion and cessation of therapy when urate-lowering efficacy is lost provide a means to optimize the safety of pegloticase in clinical practice.