Assessment of health state utilities associated with adult and pediatric acid sphingomyelinase deficiency (ASMD).

INTRODUCTION: Acid sphingomyelinase deficiency (ASMD) type B is a rare genetic disorder leading to enlargement of the spleen and liver, pulmonary dysfunction, and other symptoms. Cost-utility analyses are often conducted to quantify the value of new treatments, and these analyses require health state utilities. Therefore, the purpose of this study was to estimate utilities associated with varying levels of severity of adult and pediatric ASMD type B. METHODS: Seven adult and seven child health state vignettes describing ASMD were developed based on published literature, clinical trial results, and interviews with clinicians, patients with ASMD, and parents of children with ASMD. The health states were valued in time trade-off interviews with adult general population respondents in the UK. RESULTS: Interviews were completed with 202 participants (50.0% female; mean age = 41.3 years). The health state representing ASMD without impairment had the highest mean utility for both the adult and child health states (0.92/0.94), and severe ASMD had the lowest mean utility (0.33/0.45). Every child health state had a significantly greater utility than the corresponding adult health state. Differences between adult/child paired states ranged from 0.02 to 0.13. Subgroup analyses explored the impact of parenting status on valuation of child health states. DISCUSSION: Greater severity of ASMD was associated with lower mean utility. Results have implications for valuation of pediatric health states. The resulting utilities may be useful in cost-utility modeling estimating the value of treatment for ASMD.

Health state utilities associated with weight loss: preferences of people with type 2 diabetes and obesity in Japan.

AIMS: Health state utilities associated with weight change are needed for cost-utility analyses (CUAs) examining the value of treatments for type 2 diabetes and obesity. Previous studies have estimated the utility benefits associated with various amounts of weight reduction in the US and Europe, but preferences for weight change in Asian cultures may differ from these published values. The purpose of this study was to estimate utilities associated with reductions in body weight based on preferences of individuals with type 2 diabetes and obesity in Japan. METHODS: Health state vignettes represented type 2 diabetes with respondents' own current weight and weight reductions of 2.5%, 5%, 7.5%, 10%, 12.5%, 15%, and 20%. Utilities were elicited in time trade-off interviews with a sample of respondents in Japan with type 2 diabetes and body mass index (BMI) ≥25 kg/m2 (the cutoff for obesity in Japan). RESULTS: Analyses were conducted with data from 138 respondents (84.8% male; mean age = 58.0 years; mean BMI = 29.4 kg/m2) from all eight regions of Japan. Utility gains gradually increased with rising percentage of weight reductions ranging from 2.5% to 15%. Weight reductions of 2.5% to 15% resulted in utility increases of 0.013 to 0.048. The health state representing a 20% weight reduction yielded a wide range of preferences (mean utility increase of 0.044). Equations are recommended for estimating utility change based on any percentage of weight reduction (up to 20%) in Japanese people with type 2 diabetes and obesity. LIMITATIONS: This study was conducted in a sample with limited representation of patients with BMI >35 kg/m2 (n = 13) and relatively few women (n = 21). CONCLUSION: Results may be used to provide inputs for CUAs examining the value of treatments that are associated with weight loss in patients with type 2 diabetes and obesity in Japan.

Development of a patient-reported outcome (PRO) measure to assess patient perceptions of simplicity and complexity of treatment for type 2 diabetes.

INTRODUCTION: Treatments for type 2 diabetes vary widely in their complexity. The simplicity or complexity of a treatment regimen may have an impact on patient preference, treatment adherence, and health outcomes. The purpose of this qualitative study was to develop two draft patient-reported outcome instruments focusing on patients' experience with simplicity and complexity of treatment for type 2 diabetes. METHODS: The instruments were developed in a series of steps: gather information to support development of a concept elicitation interview guide (literature review and expert interviews), concept elicitation interviews with patients (N = 30), cognitive interviews with patients (N = 20), and a translatability assessment. RESULTS: In concept elicitation interviews, patients with type 2 diabetes reported a range of treatment attributes that influence their perceptions of treatment simplicity and complexity, such as injection devices, medication preparation, dose timing, dose frequency, ease of taking the correct dose, flexibility of dose schedule, remembering to take medication, and food requirements. Two draft questionnaires were developed based on the literature review, expert interviews, and concept elicitation interviews with patients. Revisions were made to these draft instruments based on qualitative interviews with patients and translatability assessment. DISCUSSION: The qualitative research conducted in this study supports the content validity of two newly developed instruments, the Simplicity of Diabetes Treatment Questionnaire (Sim-Q) and the Simplicity of Diabetes Treatment Questionnaire-Comparison (Sim-Q-Comp), designed to assess the simplicity and complexity of diabetes treatment from the patient's perspective.

Treatments for type 2 diabetes vary widely in their complexity, and previous research suggests that simpler treatments may have benefits for patients, such as better medication adherence and improved glycemic control. Despite the benefits of treatment simplicity, there are limited options for assessing simplicity of treatment from the patient perspective. This study was designed to develop two patient-reported outcome measures that assess simplicity and complexity of treatment for type 2 diabetes. Thirty patients with type 2 diabetes reported a range of treatment attributes that influence their perceptions of treatment simplicity and complexity. These attributes included injection devices, medication preparation, dose timing, dose frequency, ease of taking the correct dose, flexibility of dose schedule, and food requirements. Two questionnaires were developed based on literature review, expert interviews, and patient interviews (one questionnaire for rating a single treatment, and another questionnaire for comparing two treatments). Revisions were made to the draft instruments based on feedback from 20 additional participants and a translatability assessment. The resulting instruments are called the Simplicity of Diabetes Treatment Questionnaire (Sim-Q) and Simplicity of Diabetes Treatment Questionnaire-Comparison (Sim-Q-Comp). Future research with more patients is needed to further examine the psychometric properties of the questionnaires.

Development of a Patient-Reported Outcome (PRO) Measure to Assess Emotional Impact of Treatment for Type 2 Diabetes.

INTRODUCTION: Patients receiving treatment for type 2 diabetes (T2D) may experience an emotional impact associated with treatment-related changes. A patient-reported outcome (PRO) measure assessing both positive and negative emotional impact of medication treatment for T2D is needed to better understand the patient experience of treatment. The purpose of this qualitative study was to explore the emotional impact of treatment for T2D and support the development of a questionnaire to assess the emotional impact of treatment for T2D. METHODS: Exit interviews were conducted with patients with T2D participating in the SURPASS-2 and SURPASS-3 trials for tirzepatide. The exit interviews included a concept elicitation section focusing on the emotional impact of their study treatment. Results were used to develop two questionnaires that were evaluated in cognitive interviews with patients with T2D. RESULTS: The concept elicitation interviews included 28 patients (mean age 57.6 years; 64.3% female). Most patients reported positive changes in emotions associated with tirzepatide, including increased confidence (n = 23; 82.1%), hope (n = 23; 82.1%), self-esteem (n = 23; 82.1%), relief (n = 22; 78.6%), optimism (n = 21; 75.0%), sense of control (n = 21; 75.0%), happiness (n = 15; 53.6%), and motivation (n = 15; 53.6%), as well as reduced worry/anxiety (n = 19; 67.9%). Negative emotional impact was less commonly reported but included frustration (n = 2; 7.1%), worry/anxiety (n = 1; 3.6%), fear (n = 1; 3.6%), and feeling depressed (n = 1; 3.6%). Two new PROs, the Emotional Impact of Diabetes Treatment Questionnaires (EIDTQ, status and comparison versions), were developed based on these finding. The status version assesses the emotional impact of current treatment, while the comparison version allows for comparison of the current treatment to a previous treatment. The questionnaires were refined on the basis of cognitive interviews with 20 additional patients (mean age 58.3 years; 60.0% female), and results suggest that the final instruments were clear, comprehensible, and relevant to patients. CONCLUSION: The EIDTQ-Status and Comparison measures can be used as a supplement to clinical outcomes, such as hemoglobin A1c (HbA1c) and body weight, to provide a broader picture of the patient's emotional experience with medication treatment for T2D.

Medical treatment can have broad effects beyond symptom improvement, including an emotional impact. Emotional impact is subjective and therefore can only be assessed from the patient perspective. However, there is no previously published patient-reported outcome measure assessing both positive and negative emotional impact of medication treatment for type 2 diabetes. Thus, the purpose of this study was to conduct qualitative research to support the development of two new patient-reported outcome measures designed to assess the emotional impact of type 2 diabetes. Overall, the results add to previous research indicating that treatment for type 2 diabetes can have an emotional impact. The newly developed Emotional Impact of Diabetes Treatment Questionnaires were designed to assess this emotional impact, and current qualitative results support the content validity of these instruments in patients with type 2 diabetes. These instruments can be used as a supplement to clinical outcomes, such as HbA1c and body weight, to provide a broader picture of the patient's experience with medication treatment for type 2 diabetes.

Qualitative interviews to evaluate content validity of the ACTIV-2 COVID-19 Symptom Diary (ACSD).

BACKGROUND: Patient-reported outcome measures are needed to assess the impact of treatments for COVID-19 on symptoms. The ACTIV-2 COVID-19 Symptom Diary (ACSD) is being used in the ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines-2 (ACTIV-2) platform clinical trial. The purpose of the current study was to conduct qualitative interviews to assess content validity of the ACSD. METHODS: Interviews were conducted with adults who had tested positive for SARS-CoV-2. The ACSD begins with global items, followed by a symptom checklist. Each interview began with concept elicitation focusing on participant experiences with COVID-19. Then, participants completed the ACSD, and cognitive interviews were conducted to evaluate the questionnaire. Interviews were recorded, transcribed, and coded following a qualitative content analysis. For the qualitative analysis, a coding dictionary was developed with a list of all potential codes and instructions for how the codes should be applied and combined. RESULTS: Interviews were conducted with 30 participants (mean age = 39 years; 57% female; 17% Latinx; 17% Black/African American; 40% meeting at least one criterion for classification as high risk of progression to severe COVID-19). Commonly reported symptoms included fatigue (reported by 100% of the sample), body pain/muscle pain/aches (87%), headaches (87%), cough (83%), loss of smell (73%), shortness of breath/difficulty breathing (70%), and chills (70%). The 13 symptoms most commonly reported in this study are included in the ACSD. After completing the ACSD, participants consistently reported that it was clear and easy to complete, and all items were generally interpreted as intended. Based on participants' input, the ACSD was edited slightly after the first 13 interviews, and the revised version was used for the final 17 interviews. Two additional items assessing "brain fog" and dizziness were recommended for addition to the ACSD in future research. CONCLUSIONS: This qualitative study supports the content validity of the ACSD for assessment of COVID-19 symptoms. Quantitative research with larger samples will be needed to examine the questionnaire's measurement properties.

This study focused on the ACTIV-2 COVID-19 Symptom Diary (ACSD), a questionnaire that assesses symptom severity of COVID-19. The ACSD begins with global items assessing overall symptom severity, followed by a symptom checklist focusing on individual symptoms. Interviews were conducted with 30 adults who had tested positive for COVID-19. The patients reported their experiences with COVID-19, completed the ACSD, and provided their opinions about the ACSD. Based on input from these patients, the ACSD appears to be clear and easy to complete, and it includes the most common and important symptoms of COVID-19. The ACSD was edited for clarity, and "brain fog" and dizziness were recommended additions for future research. This study suggests that the ACSD is a useful questionnaire for assessment of COVID-19 symptoms in clinical studies. Studies like this are important for ensuring that symptoms are measured appropriately and accurately in clinical trials. Future research with larger samples will be needed to further examine the questionnaire.

Exit Interviews Examining the Patient Experience in Clinical Trials of Tirzepatide for Treatment of Type 2 Diabetes.

INTRODUCTION: Qualitative exit interviews can supplement clinical trial results by providing a rich and detailed picture of the patient's experience, while highlighting the treatment benefits that are meaningful to patients. Exit interviews can be particularly useful for providing insight into newer medications when less is known about the patient's subjective experience of treatment. Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist for type 2 diabetes mellitus. The purpose of this study was to conduct exit interviews with patients following participation in two trials to better understand the impact of tirzepatide from the patients' point of view. METHODS: Telephone interviews were conducted with patients with type 2 diabetes treated with tirzepatide soon after completing one of two trials (SURPASS-2, SURPASS-3). Interviews, conducted according to a semi-structured interview guide, were recorded, transcribed, and analyzed following a content analysis approach using ATLAS.ti. RESULTS: A total of 28 patients (64% female; mean age 57.6 years) completed interviews. All participants (100%) reported at least one treatment benefit. Patients provided descriptions of treatment benefits, including improved glycemic control (reported by 96% of the sample), weight loss (93%), decreased appetite (79%), and increased energy (79%), as indicated by qualitative coding. All participants said these treatment-related changes mattered to them. Patients described improvements in quality of life and daily activities associated with these treatment benefits. Despite adverse events reported by some patients (most commonly nausea, reported by 13 patients), all 28 said they would recommend tirzepatide to others, and 27 said they would be willing to continue treatment. Examples of representative quotations are presented for descriptions of treatment benefits, quality-of-life impact, and adverse events. DISCUSSION: The current results indicate that treatment benefits observed in clinical trials of tirzepatide are important to patients. As demonstrated in quotations from patients, the most enthusiastic descriptions of treatment outcomes focused on the weight loss associated with tirzepatide. The study also highlights the usefulness of exit interviews, which can supplement quantitative trial data by showing how these benefits have a meaningful impact on patients' quality of life.

Health state utilities associated with weight loss in type 2 diabetes and obesity.

INTRODUCTION: Health state utilities associated with weight change are needed as inputs for cost-utility analyses (CUAs) examining the value of treatments for obesity and type 2 diabetes (T2D). Although some pharmaceutical treatments currently in development are associated with substantial weight loss, little is known about the utility impact of weight decreases greater than 10%. The purpose of this study was to estimate utilities associated with body weight decreases up to 20% based on preferences of individuals with obesity, with and without T2D. METHODS: Health state vignettes were developed to represent respondents' own current weight and weight decreases of 2.5, 5, 10, 15, and 20%. Health state utilities were elicited in time trade-off interviews in two UK locations (Edinburgh and London) with a sample of participants with obesity, with and without T2D. Mean utility increases associated with each amount of weight decrease were calculated. Regression analyses were performed to derive a method for estimating utility change associated with weight decreases. RESULTS: Analyses were conducted with data from 405 individuals with obesity (202 with T2D, 203 without T2D). Utility increases associated with various levels of weight decrease ranged from 0.011 to 0.060 in the subgroup with T2D and 0.015 to 0.077 in the subgroup without T2D. All regression models found that the percentage of weight decrease was a highly significant predictor of change in utility (p < .0001). The relationship between weight change and utility change did not appear to be linear. Equations are recommended for estimating utility change based on the natural logarithm of percentage of weight decrease. DISCUSSION: Results of this study may be used to provide inputs for CUAs examining and comparing the value of treatments that are associated with substantial amounts of weight loss in patients with obesity, with or without T2D.

Vignette-Based Utilities: Usefulness, Limitations, and Methodological Recommendations.

Health technology assessment agencies often prefer that utilities used to calculate quality-adjusted life years in cost-utility analyses (CUAs) are derived using standardized methods, such as generic preference-based measures completed by patients in clinical trials. However, there are situations when no standardized approach is feasible or appropriate for a specific medical condition or treatment that must be represented in a CUA. When this occurs, vignette-based methods are often used to estimate utilities. A vignette (sometimes called a "scenario," "health state description," "health state vignette," or "health state") is a description of a health state that is valued in a preference elicitation task to obtain a utility estimate. This method is sometimes the only feasible way to estimate utilities representing a concept that is important for a CUA. Consequently, vignette-based studies continue to be conducted and published, with the resulting utilities used in economic models to inform decision making about healthcare resource allocation. Despite the potential impact of vignette-based utilities on medical decision making, there is no published guidance or review of this methodology. This article provides recommendations for researchers, health technology assessment reviewers, and policymakers who may be deciding whether to use vignette-based methods, designing a vignette study, using vignette-based utilities in a CUA, or evaluating a CUA that includes vignette-based utilities. Recommendations are provided on: (A) when to use vignette-based utilities, (B) methods for developing vignettes, (C) valuing vignettes, (D) use of vignette-based utilities in models, and (E) limitations of vignette methods.

Health state utilities associated with treatment process for oral and injectable GLP-1 receptor agonists for type 2 diabetes.

PURPOSE: Previous research suggests that treatment process can have an influence on patient preference and health state utilities. This study examined preferences and estimated utilities for treatment processes of two daily oral treatment regimens and two weekly injectable regimens for treatment of type 2 diabetes (T2D). METHODS: Participants with T2D in the UK reported preferences and valued four health state vignettes in time trade-off utility interviews. The vignettes had identical descriptions of T2D but differed in treatment process: (1) daily simple oral treatment (tablets without administration requirements), (2) daily oral semaglutide (with administration requirements per product label), (3) weekly dulaglutide injection, (4) weekly semaglutide injection. RESULTS: Interviews were completed by 201 participants (52.7% male; mean age = 58.7). Preferences between treatment processes varied widely. Mean utilities were 0.890 for simple oral, 0.880 for oral semaglutide, 0.878 for dulaglutide injection, and 0.859 for semaglutide injection (with higher scores indicating greater preference). All pairwise comparisons found statistically significant differences between utilities (p < 0.01), except the comparison between oral semaglutide and the dulaglutide injection (p = 0.49). CONCLUSIONS: Results suggest that routes of administration cannot be compared using only the simplest descriptions (e.g., oral versus injectable). Dose frequency and specific details of the treatment process administration had an impact on patient preference and health state utilities. The utilities estimated in this study may be useful in cost-utility models comparing these treatments for T2D. Results also suggest that it may be helpful to consider patient preferences for treatment process when selecting medications for patients in clinical settings.

A Scoring Algorithm for Deriving Utility Values from the Neuro-QoL for Patients with Multiple Sclerosis.

INTRODUCTION: The Neuro-QoL is a standardized approach to assessing health-related quality of life in people with neurological conditions, including multiple sclerosis (MS). Item banks were developed with item response theory (IRT) methodology so items are calibrated along a continuum of each construct. The purpose of this study was to develop a preference-based scoring algorithm for the Neuro-QoL to derive utilities that could be used in economic modeling. METHODS: With input from neurologists, 6 Neuro-QoL domains were selected based on relevance to MS and used to define health states for a utility elicitation study in the United Kingdom. General population participants and individuals with MS valued the health states and completed questionnaires (including Neuro-QoL short forms). The Neuro-QoL Utility Scoring System (NQU) was derived based on multi-attribute utility theory using data from the general population sample. Single-attribute disutility functions for 6 Neuro-QoL domains were estimated using isotonic regression with linear interpolation and then combined with a multiplicative model. NQU validity was assessed using MS participant data. RESULTS: Interviews were completed with 203 general population participants (50.2% female; mean age = 45.0 years) and 62 participants with MS (62.9% female; mean age = 46.1 years). Mean (SD) NQU scores were 0.94 (0.06) and 0.82 (0.13) for the general population and MS samples, respectively. The NQU demonstrated known-groups validity by differentiating among subgroups categorized based on level of disability. The NQU demonstrated convergent validity via correlations with generic measures (0.66 and 0.63 with EQ-5D-5L and Health Utilities Index Mark 3, respectively; both P < 0.001). DISCUSSION: With the NQU, utilities can be derived from any MS treatment group, subgroup, or patient sample who completes items from 6 Neuro-QoL domains. Because the Neuro-QoL is frequently used with MS patients, the NQU greatly expands the options for quantifying outcomes in cost-utility analyses conducted to inform allocation of resources for MS treatment.

Assessing patient PREFERence between the dulaglutide pen and the semaglutide pen: A crossover study (PREFER).

AIM: When selecting treatments for type 2 diabetes (T2D), it is important to consider not only efficacy and safety, but also other treatment attributes that have an impact on patient preference. The objective of this study was to examine preference between injection devices used for two weekly GLP-1 receptor agonists. MATERIALS AND METHODS: The PREFER study was an open-label, multicentre, randomized, crossover study assessing patient preference for dulaglutide and semaglutide injection devices among injection-naïve patients receiving oral medication for type 2 diabetes. After being trained to use each device, participants performed all steps of injection preparation and administered mock injections into an injection pad. Time-to-train (TTT) for each device was assessed in a subset. RESULTS: There were 310 evaluable participants (48.4% female; mean age, 60.0 years; 78 participants in the TTT subgroup). More participants preferred the dulaglutide device than the semaglutide device (84.2% vs. 12.3%; P < 0.0001). More participants perceived the dulaglutide device to have greater ease of use (86.8% vs. 6.8%; P < 0.0001). After preparing and using the devices, more participants were willing to use the dulaglutide device (93.5%) than the semaglutide device (45.8%). Training participants to use the dulaglutide device required less time than the semaglutide device (3.38 vs. 8.14 minutes; P < 0.0001). CONCLUSIONS: Participants with type 2 diabetes preferred the dulaglutide injection device to the semaglutide injection device. If patients prefer a device, they may be more willing to use the medication, which could result in better health outcomes. Furthermore, a shorter training time for injection devices may be helpful in busy clinical practice settings.

Patient Preferences and Health State Utilities Associated with Mealtime Insulin Concentrations Among Patients with Diabetes in Italy.

INTRODUCTION: Standard concentration (100 units/mL) mealtime insulin is frequently used to treat patients with type 1 (T1D) and type 2 diabetes (T2D). A more concentrated version of the medication (200 units/mL) has been available in Italy since 2016. This concentrated version is bioequivalent to the standard version and delivers the same amount of medication but in half the volume of liquid. The purpose of this study was to examine patient preferences and estimate health state utilities associated with standard and concentrated rapid-acting mealtime analog insulin. METHODS: Participants with T1D and T2D in Italy valued two health states in time trade-off interviews. The descriptions of diabetes and treatment in the two health states were identical, differing only in terms of insulin concentration (e.g., half as much liquid for the same dose, less effort needed to press the injection button, and fewer injection pens required with concentrated insulin). To ensure participants understood the health states, they were shown a short video illustrating the differences between concentrations. RESULTS: A total of 217 participants completed the interviews (49.8% male; mean age 56.1 years; 109 from Milan; 108 from Rome; 12.0% T1D; 88.0% T2D). When asked which health state they preferred, 98.2% responded the concentrated version, 0.9% said the standard version, and 0.9% had no preference. Mean [standard deviation (SD)] utilities rounded to three decimals were 0.892 (0.099) for the concentrated version and 0.884 (0.101) for the standard version. The mean (SD; p value) utility difference between the standard and concentrated rapid-acting insulin was 0.007 (0.019; p < 0.0001). CONCLUSIONS: Findings from this study provide insight into patient preferences associated with concentration of rapid-acting insulin. Although the difference in utility is small, patients consistently preferred the concentrated formulation over the standard insulin, and for some patients this difference had an impact on utility valuations. These results suggest that the concentration of rapid-acting insulin should be considered because it could affect treatment preference and quality of life. FUNDING: Eli Lilly and Company.

Health state utilities associated with treatment for transfusion-dependent ß-thalassemia.

OBJECTIVES: Transfusion-dependent ß-thalassemia (TDT) is a genetic disease that affects production of red blood cells. Conventional treatment involves regular red blood cell transfusions and iron chelation, which has a substantial impact on quality of life. While potentially curative, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with risk of complications, including graft-versus-host disease (GvHD). Gene addition therapy, a novel treatment approach, involves autologous transplantation of the patient's own genetically modified hematopoietic stem cells. The purpose of this study was to estimate utilities associated with treatment approaches for TDT. METHODS: General population respondents in England valued eight health state vignettes (developed with clinician, patient, and parent input) in time trade-off interviews. RESULTS: A total of 207 participants completed interviews (49.8% female; mean age = 43.2 years). Mean (SD) utilities for the pre-transplant health states were 0.73 (0.25) with oral chelation and 0.63 (0.32) with subcutaneous chelation. Mean utilities for the transplant year were 0.62 (0.35) for gene addition therapy, 0.47 (0.39) for allo-HSCT, and 0.39 (0.39) for allo-HSCT with acute GvHD. Post-transplant utilities were 0.93 (0.15) for transfusion independent, 0.75 (0.25) for 60% transfusion reduction, and 0.51 (0.38) for chronic GvHD. Acute and chronic GvHD were associated with significant disutility (acute = - 0.09, p < 0.0001; chronic = - 0.42, p < 0.0001). CONCLUSIONS: Utilities followed expected patterns, with logical differences between treatment options for TDT and substantially greater utility for transfusion independence than for ongoing treatment involving transfusion and chelation. These utilities may be useful in cost-utility models estimating the value of treatments for TDT.

Development of a brief clinician-reported outcome measure of multiple sclerosis signs and symptoms: The Clinician Rating of Multiple Sclerosis (CRoMS).

OBJECTIVE: No available assessment tool offers a brief and psychometrically sound way for clinicians to quantify assessment of MS in a typical office visit. The objective of this study was to develop a brief clinician-reported outcome measure of MS signs and symptoms to standardize and quantify assessments that occur during a typical neurology office visit. METHODS: A questionnaire, called the Clinician Rating of Multiple Sclerosis (CRoMS), was developed in the following steps: literature review; concept elicitation interviews (to generate questionnaire themes and content) with patients with MS (n = 14); concept elicitation interviews with neurologists (n = 9); online qualitative survey with neurologists in the US, UK, Germany, and Sweden (n = 72); online survey with neurologists to evaluate the first draft of the clinician-reported outcome measure (ClinRO) (n = 26); an in-person meeting with neurologists to discuss and revise the draft ClinRO (n = 9); and interviews with neurologists and MS nurses to further refine and finalize the ClinRO (n = 16). RESULTS: Across all steps of this research, several signs and symptoms consistently emerged as important for assessment in a typical office visit: walking, balance, upper limb function, coordination, weakness, fatigue, pain, sensory symptoms, bladder function, visual function, cognition, spasticity, spasms, and mood. The importance of these signs and symptoms was supported by neurologists during the online surveys and the in-person meeting. Neurologists were generally able to complete the draft ClinRO measure without difficulty, although minor revisions were suggested to refine the ClinRO for future use. CONCLUSION: The CRoMS may be a useful tool for efficiently assessing the severity of MS symptoms. This brief clinician-reported measure could help standardize and quantify assessments in clinical studies and clinical settings.

Developing a preference-based utility scoring algorithm for the Psoriasis Area Severity Index (PASI).

Introduction: It is challenging to identify health state utilities associated with psoriasis because generic preference-based measures may not capture the impact of dermatological symptoms. The Psoriasis Area Severity Index (PASI) is one of the most commonly used psoriasis rating scales in clinical trials. The purpose of this study was to develop a utility scoring algorithm for the PASI. Methods: Forty health states were developed based on PASI scores of 40 clinical trial patients. Health states were valued in time trade-off interviews with UK general population participants. Regression models were conducted to crosswalk from PASI scores to utilities (e.g. OLS linear, random effects, mean, robust, spline, quadratic). Results: A total of 245 participants completed utility interviews (51.4% female; mean age = 45.3 years). Models predicting utility based on the four PASI location scores (head, upper limbs, trunk, lower limbs) had better fit/accuracy (e.g. R2, mean absolute error [MAE]) than models using the PASI total score. Head/upper limb scores were more strongly associated with utility than trunk/lower limb. The recommended model is the OLS linear model based on the four PASI location scores (R2 = 0.13; MAE = 0.03). An alternative is recommended for situations when it is necessary to estimate utility based on the PASI total score. Conclusions: The derived scoring algorithm may be used to estimate utilities based on PASI scores of any treatment group with psoriasis. Because the PASI is commonly used in psoriasis clinical trials, this scoring algorithm greatly expands options for quantifying treatment outcomes in cost-effectiveness analyses of psoriasis therapies. Results indicate that psoriasis of the head/upper limbs could be more important than trunk/lower limbs, suggesting reconsideration of the standard PASI scoring approach.

Patient preferences and health state utilities associated with dulaglutide and semaglutide injection devices among patients with type 2 diabetes in Italy.

Aims: Several glucagon like peptide-1 (GLP-1) receptor agonists are available as weekly injections for treatment of type 2 diabetes. These medications vary in their injection devices, and these differences could impact quality-of-life and patient preference. The purpose of this study was to examine patient preferences and estimate health state utilities associated with injection devices for two weekly GLP-1 therapies. Materials and methods: Participants with type 2 diabetes in Italy (Milan, Rome) valued three health state vignettes in time trade-off interviews. The health states had identical descriptions of type 2 diabetes, but differed in description of the treatment process: (1) oral treatment regimen, (2) oral plus weekly dulaglutide injection, and (3) oral plus weekly semaglutide injection. Results: A total of 216 participants completed interviews (57.9% male; mean age = 60.5). Almost all patients (99.5%) preferred the oral health state over either injection health state. Comparing between the two injections, 88.4% preferred the dulaglutide health state, while 11.6% preferred the semaglutide state. Mean (SD) utilities were 0.907 (0.076) for oral, 0.894 (0.085) for dulaglutide, and 0.887 (0.087) for semaglutide. The mean (SD) utility difference between the injection device health states was 0.007 (0.019). Limitations: Although the health states were designed to match the injection device instructions for use as closely as possible, vignette-based methods are inherently limited because results are based on perceptions of the health states rather than actual patient experience with the devices. Conclusions: Results provide insight into patient preferences associated with injection devices for weekly GLP-1 receptor agonists. The majority of patients preferred the dulaglutide device over the semaglutide device, and for some patients, this difference had an impact on utility valuations. Patient preferences for injection devices could be an important factor to consider when selecting treatments for type 2 diabetes.

Development of the Diabetes Injection Device Experience Questionnaire (DID-EQ) and Diabetes Injection Device Preference Questionnaire (DID-PQ).

BACKGROUND: Previous research has examined patient perceptions of insulin injection devices. However, injectable medications other than insulin are increasingly used to treat type 2 diabetes, including GLP-1 receptor agonists. No patient-reported outcome (PRO) instruments have been developed taking into account the experiences of patients using newer injection devices, which are often different from devices used for insulin. Therefore, the purpose of this qualitative study was to develop two draft PRO instruments focusing on patients' experiences with these newer injection devices (one instrument assessing perceptions of a single injection device, and another assessing preferences between two devices). METHODS: Questionnaire development proceeded in six steps: literature review, interviews with six device experts, concept elicitation interviews with patients (N = 32), preliminary translatability assessment, cognitive interviews with patients (N = 20), and final translatability assessment. RESULTS: Literature review and expert interviews were conducted to inform a concept elicitation interview guide. In concept elicitation in the US, UK, and Germany, patients with type 2 diabetes reported a range of injection features that influenced their perceptions of non-insulin injection devices (e.g., requirements for preparation of the medication/device, issues related to the needle, ease-of-use, portability). Two draft "item pools" were developed based on the literature review, expert interviews, and concept elicitation results. In cognitive interviews, patients recommended minor revisions and indicated that the draft instruments were generally clear, comprehensible, and relevant to their experience with non-insulin injectable medication. The instruments were refined based on the cognitive interviews and translatability assessment, resulting in two questionnaires. CONCLUSIONS: The various steps of qualitative research support the content validity of these new PRO instruments, which are the first developed specifically to assess perceptions of non-insulin injection delivery systems. Despite some overlap with insulin-focused questionnaires, the new instruments are distinct from previous instruments (omitting content that would not be relevant to patients receiving non-insulin injectable treatment, while including content that is not included in the insulin focused instruments). This qualitative research yielded two draft questionnaires that are grounded in patient perceptions and ready for psychometric validation studies with larger samples of patients with type 2 diabetes.

Psychometric evaluation of the Diabetes Injection Device Experience Questionnaire (DID-EQ) and Diabetes Injection Device Preference Questionnaire (DID-PQ).

BACKGROUND: Previous research has examined patient perceptions of insulin injection devices. However, a range of injectable medications other than insulin are now used to treat type 2 diabetes. No patient-reported outcome (PRO) instruments have been developed taking into account the perceptions of patients using newer injection devices, which are often different from those used in the past. Therefore, the primary purpose of this study was to evaluate a new PRO instrument focusing on patients' experiences with injection devices, including those used for newer treatments such as GLP-1 receptor agonists. METHODS: Patients with T2D treated with non-insulin injectable medications were recruited via advertisements and six clinical sites in the US. All participants completed the draft Diabetes Injection Device - Experience Questionnaire (DID-EQ) and additional measures administered for validity assessment. Participants who had experience with two non-insulin injection devices also completed the draft Diabetes Injection Device - Preference Questionnaire (DID-PQ). Analyses focused on item reduction (item performance, exploratory factor analysis), reliability, and validity. RESULTS: One hundred fourty two patients (mean age = 63.0y; 56.3% female) participated. Item reduction yielded a 10-item version of the DID-EQ, including a 7-item Device Characteristics subscale and three global items assessing satisfaction, ease of use, and convenience of the injection device. The DID-EQ demonstrated good internal consistency reliability (Cronbach's alpha of Device Characteristics subscale = 0.80) and 7-day test-retest reliability (ICCs: 0.92 for Device Characteristics subscale; 0.65 to 0.91 for the three global items). Construct validity was demonstrated via correlations with previously validated instruments (e.g., correlations with the DTSQ treatment satisfaction subscale ranged from 0.56 to 0.60, all p < 0.0001; correlations with the TRIM-D Device ranged from 0.63 to 0.77, all p < 0.0001). Descriptive analyses of the DID-PQ were conducted with a subset of 27 participants who were able to use it to compare two devices. CONCLUSIONS: This psychometric evaluation supports the reliability and validity of the DID-EQ, while providing initial information on the performance of the DID-PQ. These brief questionnaires complement measures of treatment efficacy and provide a more thorough picture of patients' experiences with non-insulin injectable treatments for type 2 diabetes.

Patient preferences in Italy: health state utilities associated with attributes of weekly injection devices for treatment of type 2 diabetes.

OBJECTIVES: Several glucagon-like peptide-1 receptor agonists are administered as weekly injections for treatment of type 2 diabetes (T2D). These medications vary in their injection processes, and a recent study in the UK found that these differences had an impact on patient preference and health state utilities. The purpose of this study was to replicate the UK study in Italy to examine preferences of an Italian patient sample, while allowing for comparison between utilities in the UK and Italy. MATERIALS AND METHODS: Participants with T2D in Italy valued health states in time trade-off interviews. All health states had the same description of T2D, but differed in description of the treatment process. As in the original UK study, the first health state described an oral treatment regimen, while additional health states added a weekly injection. The injection health states differed in three injection-related attributes: requirements for reconstituting the medication, waiting during medication preparation, and needle handling. RESULTS: Interviews were completed by 238 patients (58.8% male; mean age = 60.2 years; 118 from Milan, 120 from Rome). The oral treatment health state had a mean (SD) utility of 0.90 (0.10). The injection health states had significantly (p < 0.0001) lower utilities, which ranged from 0.87 (requirements for reconstitution, waiting, and handling) to 0.89 (weekly injection with none of these requirements). Differences in health state utility scores suggest that each administration requirement was associated with a disutility (ie, negative utility difference): -0.006 (reconstitution), -0.006 (needle handling), -0.011 (reconstitution, needle handling), and -0.022 (reconstitution, waiting, needle handling). CONCLUSION: Disutilities associated with the injection device characteristics were similar to those reported with the UK sample. Results suggest that injection device attributes may be important to some patients with T2D, and it may be useful for clinicians to consider these attributes when choosing medication for patients initiating these weekly treatments.

Health state utilities associated with attributes of weekly injection devices for treatment of type 2 diabetes.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are often recommended as part of combination therapy for type 2 diabetes when oral medication does not result in sufficient glycemic control. Several GLP-1 receptor agonists are available as weekly injections. These medications vary in their injection delivery systems, and these differences could impact quality of life and treatment preference. The purpose of this study was to estimate utilities associated with attributes of injection delivery systems for weekly GLP-1 therapies. METHODS: Participants with type 2 diabetes in the UK valued health states in time trade-off interviews. The health states (drafted based on literature, device instructions for use, and clinician interviews) had identical descriptions of type 2 diabetes, but differed in description of the treatment process. One health state described oral treatment, while six others described oral treatment plus a weekly injection. The injection health states varied in three aspects of the treatment administration process: requirements for reconstituting the medication (i.e., mixing the medication prior to the injection), waiting during medication preparation, and needle handling. Every participant valued all seven health states. RESULTS: A total of 209 participants completed interviews (57.4% male; mean age = 60.4y). The mean utility of the oral treatment health state was 0.89. All injection health states had significantly (p < 0.01) lower utilities ranging from 0.86 to 0.88. Differences among health state utilities suggest that each administration requirement had a small but measureable disutility: -0.004 (reconstitution), -0.004 (needle handling), -0.010 (reconstitution, needle handling), and -0.020 (reconstitution, waiting, needle handling). CONCLUSIONS: Findings suggest it is feasible to use the TTO method to quantify preferences among injection treatment processes. It may be useful to incorporate these utility differences into cost-utility models comparing weekly injectable treatments for patients with type 2 diabetes.