Impact of Elexacaftor/Tezacaftor/Ivacaftor on Healthcare Resource Utilization and Associated Costs Among People With Cystic Fibrosis in the US: A Retrospective Claims Analysis.

INTRODUCTION: Cystic fibrosis (CF) is a life-limiting genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is a CFTR modulator (CFTRm) that targets the underlying cause of CF. Based on safety and efficacy demonstrated in clinical trials, ELX/TEZ/IVA is approved in the US for the treatment of CF in people aged ≥ 2 years who have ≥ 1 F508del-CFTR mutation or a CFTR mutation that is responsive to ELX/TEZ/IVA based on in vitro data. While ELX/TEZ/IVA demonstrated unprecedented improvements in lung function and dramatic reductions in pulmonary exacerbations (PEx) and associated hospitalizations in clinical trials, a limited number of studies have examined the impact of ELX/TEZ/IVA on healthcare resource utilization (HCRU) and associated costs in a real-world setting. The aim of this retrospective study was to evaluate changes in PEx, HCRU, and associated non-CFTRm healthcare costs following initiation of ELX/TEZ/IVA among people with CF aged ≥ 12 years in the US. METHODS: We evaluated the rates of PEx, HCRU, and associated costs before and after initiation of ELX/TEZ/IVA in people with CF aged ≥ 12 years using data from the Merative MarketScan® Commercial Claims and Encounters Database and the Merative Multi-State Medicaid Database from April 21, 2019 to December 31, 2020. Because the study period included time following the onset of the COVID-19 pandemic, we limited our primary analysis to the period prior to the pandemic (October 21, 2019 to March 12, 2020). Outcomes following the onset of the pandemic (March 13 to December 31, 2020) were examined in an exploratory analysis. RESULTS: In both commercially insured and Medicaid-insured people with CF, ELX/TEZ/IVA was associated with reductions in PEx, hospitalizations, and associated costs prior to the COVID-19 pandemic, and these reductions were maintained following the onset of the pandemic. CONCLUSIONS: These findings suggest that ELX/TEZ/IVA reduces the burden and costs associated with PEx and hospitalizations in people with CF.

EFFECT OF ELEXACAFTOR/TEZACAFTOR/IVACAFTOR ON ANNUAL RATE OF LUNG FUNCTION DECLINE IN PEOPLE WITH CYSTIC FIBROSIS.

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be safe and efficacious in people with cystic fibrosis (CF) with ≥ 1 F508del-CFTR allele in Phase 3 clinical trials. ELX/TEZ/IVA treatment led to improved lung function, with increases in percent predicted forced expiratory volume in 1 second (ppFEV1) and Cystic Fibrosis Questionnaire-Revised respiratory domain score. Here, we evaluated the impact of ELX/TEZ/IVA on the rate of lung function decline over time by comparing changes in ppFEV1 in participants from the Phase 3 trials with a matched group of people with CF from the US Cystic Fibrosis Foundation Patient Registry not eligible for cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy. Participants treated with ELX/TEZ/IVA had on average no loss of pulmonary function over a 2-year period (mean annualized rate of change in ppFEV1, +0.39 percentage points [95% CI, -0.06 to 0.85]) compared with a 1.92 percentage point annual decline (95% CI, -2.16 to -1.69) in ppFEV1 in untreated controls. ELX/TEZ/IVA is the first CFTR modulator therapy shown to halt lung function decline over an extended time period.

Non-respiratory health-related quality of life in people with cystic fibrosis receiving elexacaftor/tezacaftor/ivacaftor.

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be safe and efficacious in people with cystic fibrosis (CF) heterozygous for F508del and a minimal function mutation (F/MF) or homozygous for F508del (F/F) in two pivotal Phase 3 trials, significantly improving percentage predicted forced expiratory volume in 1 second, Cystic Fibrosis Questionnaire-Revised, Respiratory Domain (CFQ-R RD) scores, and sweat chloride concentration. Here, we analyzed the 11 non-respiratory domains (non-RDs) of the CFQ-R, which assess general health-related quality of life (i.e., Physical Functioning, Role Functioning, Vitality, Health Perceptions, Emotional Functioning, and Social Functioning) and quality of life impacted by CF (i.e., Body Image, Eating Problems, Treatment Burden, Weight, and Digestive Symptoms), for participants in these two Phase 3 trials. ELX/TEZ/IVA treatment led to higher scores in all CFQ-R non-RDs, with improvements in most domains compared with control treatments. These findings demonstrate that ELX/TEZ/IVA improves a range of CF-specific symptoms and general functioning and well-being.

Disease burden in people with cystic fibrosis heterozygous for F508del and a minimal function mutation.

BACKGROUND: People with cystic fibrosis (CF) heterozygous for F508del-CFTR and a minimal function CFTR mutation (F/MF) that results in no CFTR protein or results in CFTR protein that is not responsive to tezacaftor, ivacaftor, and tezacaftor/ivacaftor in vitro comprise a sizeable percentage of the US CF population. This retrospective, cross-sectional, observational study aimed to characterize CF burden in this subpopulation. METHODS: People ≥2 years of age in the US CF Foundation Patient Registry with a CF diagnosis, F/MF genotype, and ≥1 encounters in 2017 were included. Descriptive analyses assessed lung function, nutritional parameters, microbiology, hospitalization and pulmonary exacerbation rates, and CF-related complications. Results were stratified by age group; select characteristics were summarized by percent predicted FEV1 (ppFEV1) and ethnicity. RESULTS: 5348 people met inclusion criteria. Rates of positive bacterial cultures, pulmonary exacerbations, and hospitalizations were generally higher in older age groups. Prevalence of prescribed symptomatic CF therapies was substantial and also generally higher in older age groups. ppFEV1 was lower in older age groups. A greater percentage of adolescents and adults reported complications, including cirrhosis, osteoporosis, osteopenia, and sinus disease, than younger age groups. Increased prevalence of cultured Pseudomonas aeruginosa and prescribed chronic therapy was seen with decreasing ppFEV1. In each age group, ppFEV1 was slightly higher in the non-Hispanic cohort than in the Hispanic cohort. CONCLUSIONS: People with F/MF genotypes have substantial disease burden that worsened in older age groups consistent with the progressive nature of CF, indicating need for additional treatment options in this subpopulation.

The Trend of High-Dose Insulin Usage Among Patients with Diabetes in the UK: A Retrospective Study.

INTRODUCTION: Many patients with diabetes may require high-dose insulin treatment to achieve target HbA1c level, but the prevalence, disease burden, and patient characteristics of the population remain unclear. We therefore investigated people with insulin-treated diabetes in the UK from 2009 to 2013, who were prescribed high daily doses (> 200 units/day). METHODS: A retrospective analysis was conducted using the UK primary care electronic dataset from the Clinical Practice Research Datalink (CPRD). Trends of demographics, insulin dose, clinical characteristics, and annualized incidence rate of the insulin initiators were analyzed. Patients with type 1 (T1D) or type 2 diabetes (T2D) and who were prescribed insulin between 2009 and 2013 were categorized into either a low- or high-dose insulin user group. Two-sample t test and chi-square test were used for comparison of continuous variables and categorical variables, respectively. A multivariable negative binomial regression analysis with (log) person time as an offset was used to assess the impact of different covariates on incidence of high-dose insulin initiation. RESULTS: Between 2009 and 2013, 19,631 patients with diabetes were treated with insulin (T1DM, 7620; T2DM, 12,011). In 2013, 415 high-dose insulin initiators were identified (T1DM, N = 170; T2DM, N = 245). More than half were male (T1DM/T2DM, 62.4%/56.3%) and 94.1%/83.7% of T1DM/T2DM patients were prescribed an insulin analogue at high-dose insulin initiation. At 6 months, 43.6% of T1DM and 42.6% of T2DM remained to have suboptimal HbA1c level of ≥ 8% (64 mmol/mol). Overall, 15.9%/63.3% of high-dose insulin initiators (HDII) with T1DM/T2DM took oral antidiabetics. From 2009 to 2013, the estimated glomerular filtration rate worsened in both T1DM and T2DM HDII. CONCLUSION: Despite a number of patients requiring high doses of insulin in the UK, achievement of optimal HbA1c levels remains poor. Early identification of HDII is important in order to plan for alternative/adjuvant antidiabetic and lifestyle strategies to achieve optimal glycemic targets in this patient group. FUNDING: Eli Lilly and Company.

Treating Type 1 Diabetes Mellitus with a Rapid-Acting Analog Insulin Regimen vs. Regular Human Insulin in Germany: A Long-Term Cost-Effectiveness Evaluation.

OBJECTIVE: The aim of the present study was to evaluate the cost effectiveness of rapid-acting analog insulin relative to regular human insulin in adults with type 1 diabetes mellitus in Germany. METHODS: The PRIME Diabetes Model, a patient-level, discrete event simulation model, was used to project long-term clinical and cost outcomes for patients with type 1 diabetes from the perspective of a German healthcare payer. Simulated patients had a mean age of 21.5 years, duration of diabetes of 8.6 years, and baseline glycosylated hemoglobin of 7.39%. Regular human insulin and rapid-acting analog insulin regimens reduced glycosylated hemoglobin by 0.312 and 0.402%, respectively. Compared with human insulin, hypoglycemia rate ratios with rapid-acting analog insulin were 0.51 (non-severe nocturnal) and 0.80 (severe). No differences in non-severe diurnal hypoglycemia were modeled. Discount rates of 3% were applied to future costs and clinical benefits accrued over the 50-year time horizon. RESULTS: In the base-case analysis, rapid-acting analog insulin was associated with an improvement in quality-adjusted life expectancy of 1.01 quality-adjusted life-years per patient (12.54 vs. 11.53 quality-adjusted life-years). Rapid-acting analog insulin was also associated with an increase in direct costs of €4490, resulting in an incremental cost-effectiveness ratio of €4427 per quality-adjusted life-year gained vs. human insulin. Sensitivity analyses showed that the base case was driven predominantly by differences in hypoglycemia; abolishing these differences reduced incremental quality-adjusted life expectancy to 0.07 quality-adjusted life-years, yielding an incremental cost-effectiveness ratio of €74,622 per quality-adjusted life-year gained. CONCLUSIONS: Rapid-acting analog insulin is associated with beneficial outcomes in patients with type 1 diabetes and is likely to be considered cost effective in the German setting vs. regular human insulin.

Behaviours, thoughts and perceptions around mealtime insulin usage and wastage among people with type 1 and type 2 diabetes mellitus: A cross-sectional survey study.

AIMS: People with diabetes who use mealtime insulin (MTI) were surveyed about insulin wastage and injection habits when insufficient insulin remains in a disposable prefilled pen/cartridge to administer a full dose in a single injection. METHODS: Cross-sectional, online, self-reported survey of MTI usage/wastage behaviour in 400 adults with type 1 (n=120) or type 2 (n=280) diabetes mellitus administering >20units/day of MTI via 100units/ml prefilled pens/cartridges for ⩾1month, conducted in France, Germany, Italy and UK. RESULTS: Participants' mean±standard deviation age was 54.5±12.2years, body mass index was 29.9±7.2kg/m2 and duration of MTI therapy was 8.6±7.8years. They administered 3.7±5.9 injections/day with meals, using 11.3±18.0 prefilled pens/cartridges per month. Overall, 63.5% split the dose across two prefilled pens/cartridges (i.e. administered two injections to obtain a full dose), 15.0% used just what remained in their current pen (i.e. took a lower-than-prescribed dose) and 36.3% discarded prefilled pens/cartridges still containing insulin (i.e. took full dose with new pen). The latter participants discarded a mean 5.5±8.2 prefilled pens/cartridges monthly still containing insulin, each containing 8.6±8.7 units of insulin. Participants who wasted insulin considered it frustrating, time-consuming and painful to inject twice. CONCLUSIONS: Patients taking >20units/day MTI can find transitions between insulin pens challenging. This study highlights the need to identify ways of improving transitions between pens to make transitions easier for insulin users, which could potentially improve adherence to prescribed doses and reduce waste.

Basal-bolus Therapy in Patients with Type 2 Diabetes Mellitus in the UK: Patient Characteristics, Treatment Patterns and the Effect of Switching to Premixed Insulin.

INTRODUCTION: Increasing emphasis is being placed on insulin use among patients with type 2 diabetes mellitus (T2DM). Basal-bolus (BB) therapy is regarded as the gold standard, but a high frequency of injections and the general complexity of this therapy are seen as barriers in real-world practice. Here we describe the characteristics and treatment patterns of patients with T2DM receiving BB in the UK, with specific focus on those switching to a simplified regimen of premixed insulin. METHODS: Patients with T2DM receiving BB from 1 January 2005 were identified from the Clinical Practice Research Datalink. Characteristics were described at treatment initiation or on 1 January 2005, and treatment patterns were assessed at 12 months of follow-up. Clinical factors were compared in two groups of patients who while receiving BB had one haemoglobin A1c (HbA1c) measurement of ≥53 mmol/mol (7.0%) and remained either on BB or switched to a premixed insulin regimen. RESULTS: Study criteria were met by 12,060 subjects (mean age 59 years; duration diabetes 12.4 years). The mean HbA1c concentration was 76 mmol/mol (9.1% of patients), and 84.0% of patients were overweight. At 12 months of follow-up, 74.5% of the patients who had started BB remained on it. While on BB, 8835 patients had a HbA1c measurement of ≥53 mmol/mol (7.0% of all patients); of these, 95.9% remained on BB and 4.1% switched to premixed insulin. Mean HbA1c levels were consistently higher for patients who switched to premixed insulin than for those who remained on BB, but the levels remained relatively unchanged over time. CONCLUSION: A large proportion of patients receiving insulin did not achieve good glycaemic control in clinical practice. A small subset with higher comorbidities and HbA1c levels switched to a simplified regimen. Little evidence was found that type of insulin therapy was associated with meaningful changes in key clinical factors over time. FUNDING: Eli Lilly and company.

Attributes Influencing Insulin Pen Preference Among Caregivers and Patients With Diabetes Who Require Greater Than 20 Units of Mealtime Insulin.

BACKGROUND: This study compared patient preference for Humalog® KwikPen™ 200 units/mL (insulin lispro; hereafter, IL 200 pen; Eli Lilly and Company, Indianapolis, IN) versus the Humalog KwikPen 100 units/mL (insulin lispro; hereafter, IL 100 pen; Eli Lilly and Company, Indianapolis, IN) in patients with diabetes requiring >20 units of mealtime insulin and diabetes caregivers. This study also determined which attributes had the greatest influence on pen preference selection. METHODS: In this 2-period, crossover, simulated-use study, 106 participants were randomized to 1 of 8 sequences that varied the pen order (IL 100 pen or IL 200 pen) and dosing order (15 units = low dose or 50 units = high dose) for a total of 4 simulated injections. Participants then completed a self-administered questionnaire to select their overall preference between the 2 pens and then rated the importance of 11 pen attributes in contributing to their overall preference. RESULTS: Of the 90 participants expressing an overall preference, significantly more preferred the IL 200 pen to the IL 100 pen (IL 200 pen: 80 respondents; IL 100 pen: 10 respondents; 95% confidence interval [0.81, 0.94], P < .0001). The total amount of insulin in the pen, the ease in pressing the injection button, and the amount of fluid injected were key attributes influencing IL 200 pen preference. CONCLUSIONS: Based on these key attributes, the IL 200 pen was significantly preferred over the IL 100 pen by patients with diabetes who require >20 daily mealtime insulin units or diabetes caregivers and may improve the injection experience for these patients.

Insulin dosing and outcomes among commercially insured patients with type 2 diabetes in the United States.

PURPOSE: The purpose of this study was to examine costs, resource use, adherence, and hypoglycemic events among patients with type 2 diabetes mellitus (T2DM) treated with increasing doses of 100-U/mL (U-100) insulin regimens. METHODS: Data from Truven's Health Analytics Commercial Claims and Encounters database from January 1, 2008, through January 31, 2011, were used. Regressions were used to examine the associations among costs, resource use, adherence, and receipt of a hypoglycemic event and index dose of insulin. Specifically, general linear models with a γ-distribution and log link were used to examine costs, whereas logistic and negative binomial regressions were used to examine resource use and hypoglycemic events. All analyses controlled for patient characteristics, preindex comorbidities, general health, use of antidiabetic medications, and visits to an endocrinologist. FINDINGS: The study focused on 101,728 individuals with T2DM who received an outpatient prescription for U-100 insulin. In general, costs and resource use are highest among patients treated with the highest dose of insulin (>300 U/d). For example, all-cause and diabetes-related hospitalizations and office visits were highest in the highest-dose cohort. Costs generally followed the same pattern. Patients who were prescribed the lowest dose of insulin (10-100 U/d) generally had higher all-cause or diabetes-related inpatient and emergency department costs and resource use compared with those patients with an index dose >100 to 150, >150 to 200, and >200 to 300 U/d. There were generally no significant differences in rates of hypoglycemic events based on index dose. IMPLICATIONS: These results suggest significant differences in patient outcomes based on dosing of insulin. Those patients with T2DM using insulin at the highest and lowest dose ranges have the highest costs and resource use.

Dosing of U-100 insulin and associated outcomes among Medicare enrollees with type 1 or type 2 diabetes.

OBJECTIVE: To examine costs, resource utilization, adherence, and hypoglycemic events among various doses of U-100 insulin regimens among elderly patients (age ≥65 years) diagnosed with diabetes. METHODS: Truven Health Analytics Medicare databases from January 1, 2008 through December 31, 2011 were utilized. General linear models with a gamma distribution and log link were used to examine costs, while logistic and negative binomial regressions were used to examine resource utilization and hypoglycemic events. Analyses controlled for patient characteristics, pre-period comorbidities, general health, and use of antidiabetic medications as well as index dose of insulin. RESULTS: All-cause inpatient, emergency room, and outpatients costs, as well as diabetes-related inpatient costs, were highest among individuals who were treated with an index dose of 10-100 units/day followed by >300 units/day, while drug costs and total costs generally increased as index dosage increased. Resource utilization generally followed the same pattern as costs, with number of office visits increasing as the dose increased and the highest hospital length of stay, number of hospitalizations, number of emergency room visits, and number of diabetes-related hospitalizations were generally highest among those in the lowest and highest index dose cohorts. Compared to patients who initiated with an index dose of 10-100 units/day, all other patients were significantly less likely to achieve an adherence threshold of 80% based upon index dose range, and while those with an index dose of >100-150 units/day were significantly more likely to experience a hypoglycemic event. CONCLUSION: These results suggest that, for elderly individuals with diabetes, there is a higher patient burden among those who receive the lowest and highest insulin doses.

Safe and Effective Use of the Once Weekly Dulaglutide Single-Dose Pen in Injection-Naïve Patients With Type 2 Diabetes.

BACKGROUND: This 4-week, phase 3b, multicenter, open-label, single-arm, outpatient study demonstrated the safe and effective use of the dulaglutide single-dose pen containing 0.5 mL of placebo for subcutaneous injection in injection-naïve adult patients with type 2 diabetes (T2D), with A1C ≤ 8.5% (69 mmol/mol), BMI ≥ 23 kg/m2 and ≤ 45 kg/m(2). METHOD: Patients completed a modified self-injecting subscale of the Diabetes Fear of Injecting and Self-Testing Questionnaire (mD-FISQ) and were trained to self-inject with the single-dose pen. Patients completed the initial self-injection at the site, injected at home for 2 subsequent weeks, and returned to the site for the final injection. The initial and final self-injections were evaluated for success; the final (initial) self-injection success rate was the primary (secondary) outcome measure, and the primary (secondary) objective was to demonstrate this success rate as being significantly greater than 80%. Patients recorded their level of pain after each injection. After the final injection, patients completed the mD-FISQ and the Medication Delivery Device Assessment Battery (MDDAB) to assess their perceptions of the single-dose pen, including ease of use and experience with the device. RESULTS: Among 211 patients (mean age: 61 years), the primary objective was met, with a final injection success rate of 99.1% (95% CI: 96.6% to 99.7%). Among 214 patients, the initial injection success rate was 97.2% (95% CI: 94.0% to 98.7%), meeting the key secondary objective. Overall, most patients (>96%) found the device easy to use, were satisfied with the device, and would be willing to continue to use the single-dose pen after the study. There was a significant reduction (P < .001) from baseline to study end in patients' fear of self-injecting, as measured by the mD-FISQ. CONCLUSIONS: The dulaglutide single-dose pen was found to be a safe and effective device for use by patients with T2D who were injection-naïve. A positive injection experience is an important factor for patients and providers when initiating injectable therapy.

Health state utilities for skeletal-related events secondary to bone metastases.

INTRODUCTION: Patients with bone metastases often experience skeletal-related events (SREs). Although cost-utility models are used to examine treatments for metastatic cancer, limited information is available on utilities of SREs. The purpose of this study was to estimate the disutility of four SREs: spinal cord compression, pathological fracture, radiation to bone, and surgery performed to stabilize a bone. METHODS: General population participants from the UK and Canada completed time trade-off (TTO) interviews to assess the utility of health states drafted based on literature review, clinician interviews, and patient interviews. Respondents first rated a health state describing cancer with bone metastases. Then, the SREs were added to this health state. RESULTS: Interviews were completed with 187 participants (50.8 % male, 80.2 % white). Cancer with bone metastases without an SRE had a mean utility of 0.47 (SD = 0.43) on a standard utility scale (1 = full health, 0 = death). Of the SREs, spinal cord compression was associated with the greatest disutility (i.e., the utility decrease): -0.32 with paralysis and -0.22 without paralysis. Surgery had a disutility of -0.07. Leg, arm, and rib fractures had disutilities of -0.06, -0.04, and -0.03. Two weeks of daily radiation treatment had a disutility of -0.06, while two radiation appointments had the smallest impact on utility (-0.02). CONCLUSION: All SREs were associated with statistically significant utility decreases, suggesting a perceived impact on quality of life beyond the impact of cancer with bone metastases. The resulting disutilities may be used in cost-utility models examining treatments to prevent SREs secondary to bone metastases.

Insulin use in long term care settings for patients with type 2 diabetes mellitus: a systematic review of the literature.

OBJECTIVE: To summarize currently available data about insulin therapy in patients with diabetes mellitus (DM), focusing on patients with type 2 DM (T2DM), in long term care (LTC) settings. DATA SOURCES: Ovid Medline, EMBASE, Cochrane Library databases, and United Kingdom National Health Service (NHS) Economic Evaluation Database, last accessed on November 12, 2012. STUDY ELIGIBILITY CRITERIA: We included studies that reported insulin use in patients with T2DM, and studies with combined samples of patients with type 1 DM or T2DM, that were conducted in LTC settings. Excluded were review articles and studies published before 2000. RESULTS: We identified 11 articles that met all inclusion and exclusion criteria. Insulin use in patients with DM in LTC settings varied widely, from 2.7% to 58.0%. It is difficult to draw conclusions from these proportions, as many studies did not define whether their populations were exclusively patients with T2DM. Despite recommendations against its use by the American Diabetes Association, the American Geriatrics Society, and the American Medical Directors Association, treatment with sliding-scale insulin (insulin injections adjusted to current blood glucose levels) was prevalent in the LTC setting. Although the recommended target hemoglobin A1c (A1C) for this patient population varies from ≤6.5% to ≤8.0%, higher A1C values (8.0%-8.9%) were associated with better patient outcomes in a study examining insulin treatment in community-dwelling elderly patients enrolled in an outpatient LTC setting. Insulin pen-devices seemed associated with a high incidence of needle-stick injuries in workers in LTC settings but, compared with insulin vials, showed cost advantages for use in very short-term (≤30 days) patients with DM in LTC settings. LIMITATIONS: Paucity of available data; only published studies for which full-text articles could be retrieved and which were identified by our search strategy were included; insufficient detail about patient samples were available in many included studies; and potential biases across studies might be introduced by funding sources or study designs. CONCLUSIONS: Available data about insulin therapy in patients with DM in LTC settings are very scarce and great treatment variability of this patient population seems to prevail in the current clinical practice. Additional, randomized, prospective clinical trials are needed to expand our knowledge and allow clinicians to make informed treatment decisions for patients with DM in LTC settings.

Utilities associated with subcutaneous injections and intravenous infusions for treatment of patients with bone metastases.

INTRODUCTION: Although cost-utility models are often used to estimate the value of treatments for metastatic cancer, limited information is available on the utility of common treatment modalities. Bisphosphonate treatment for bone metastases is frequently administered via intravenous infusion, while a newer treatment is administered as a subcutaneous injection. This study estimated the impact of these treatment modalities on health state preference. METHODS: Participants from the UK general population completed time trade-off interviews to assess the utility of health state vignettes. Respondents first rated a health state representing cancer with bone metastases. Subsequent health states added descriptions of treatment modalities (ie, injection or infusion) to this basic health state. The two treatment modalities were presented with and without chemotherapy, and infusion characteristics were varied by duration (30 minutes or 2 hours) and renal monitoring. RESULTS: A total of 121 participants completed the interviews (52.1% female, 76.9% white). Cancer with bone metastases had a mean utility of 0.40 on a standard utility scale (1 = full health; 0 = dead). The injection, 30-minute infusion, and 2-hour infusion had mean disutilities of -0.004, -0.02, and -0.04, respectively. The mean disutility of the 30-minute infusion was greater with renal monitoring than without. Chemotherapy was associated with substantial disutility (-0.17). When added to health states with chemotherapy, the mean disutilities of injection, 30-minute infusion, and 2-hour infusion were -0.02, -0.03, and -0.04, respectively. The disutility associated with injection was significantly lower than the disutility of the 30-minute and 2-hour infusions (P < 0.05), regardless of chemotherapy status. CONCLUSION: Respondents perceived an inconvenience with each type of treatment modality, but injections were preferred over infusions. The resulting utilities may be used in cost-utility models examining the value of treatments for the prevention of skeletal-related events in patients with bone metastases.

Patient-reported outcome instruments used to assess pain and functioning in studies of bisphosphonate treatment for bone metastases.

PURPOSE: When treating metastatic bone disease, relief of bone pain is often a key outcome. Because pain cannot be quantified with objective clinical measures, patient-reported outcome (PRO) measures are required to assess patients' subjective experience. The goal of the current review was to examine measures used to assess pain, as well as the impact of pain on functional status and health-related quality of life (HRQL), in trials of bisphosphonates for the treatment of bone metastases. METHODS: A literature search focused on articles published from January 1999 to April 2009. RESULTS: A total of 49 articles were located that used PROs to assess pain-related outcomes of bisphosphonate treatment for bone metastases. The Brief Pain Inventory was the most commonly used multi-item instrument. However, the most common approach for assessing pain was to administer a single-item scale such as a visual analog scale, numerical rating scale, or verbal rating scale. Of the 49 studies, 19 included a PRO assessing functional status or HRQL. CONCLUSIONS: Although pain is an important outcome of trials examining treatment for bone metastases, the current review suggests that there is little consistency in PRO measurement across studies. Furthermore, presentation of measures often lacked clear description, information on measurement properties, citations, clarity regarding method of administration, and consistent instrument names. Recommendations are provided for instrument validation within the target population, assessment of content validity, use of PRO instruments recently developed for patients with bone metastases, clear description of instruments, and implementation of measures consistent with recommendations from instrument developers.

Preferences related to attention-deficit/hyperactivity disorder and its treatment.

OBJECTIVES: A growing body of literature has highlighted the importance of considering patient preferences as part of the medical decision-making process. The purpose of the current review was to identify and summarize published research on preferences related to attention-deficit/hyperactivity disorder (ADHD) and its treatment, while suggesting directions for future research. METHODS: A literature search identified 15 articles that included a choice-based assessment of preferences related to ADHD. RESULTS: The 15 studies were grouped into four categories based on preference content: preference for a treatment directly experienced by the respondent or the respondent's child; preference for general treatment approaches; preference for a specific treatment attribute or outcome; and preference for aspects of ADHD-related treatment. Preference assessment methods ranged from global single items to detailed choice-based procedures, with few studies using rigorously developed assessment methods. Respondents included patients with ADHD, clinicians, parents, teachers, and survey respondents from the general population. Factors influencing preference include treatment characteristics, effectiveness for specific symptoms, side effects, and respondent demographics. Minimal research has examined treatment preferences of adults with ADHD. DISCUSSION: Because there is no dominant treatment known to be the first choice for all patients, ADHD is a condition for which individual preferences can play an important role when making treatment decisions for individual patients. Given the potential role of preferences in clinical decision-making, more research is needed to better understand the preferences of patients with ADHD and other individuals who are directly affected by the disorder, such as parents and teachers.

Utilities and disutilities for attributes of injectable treatments for type 2 diabetes.

INTRODUCTION: Although cost-utility models are frequently used to estimate treatment outcomes for type 2 diabetes, utilities are not available for key attributes of injectable treatments. The purpose of this study was to identify the utility or disutility of three injection-related attributes (dose frequency, dose flexibility, injection site reaction) that may influence patient preference. METHODS: Patients with type 2 diabetes in Scotland completed standard gamble (SG) interviews to assess the utility of hypothetical health states and their own current health state. The EQ-5D, PGWB, IWQOL-Lite, and QIDS were also administered. Construct validity and differences among health states were examined. RESULTS: A total of 151 patients completed interviews. Of the three injection-related attributes, dose frequency was the only attribute with a statistically significant impact on utility (in a multiple regression model, p = 0.01). Weekly injections were associated with an average added utility of 0.023 in comparison to everyday injections. Flexible dosing and injection site reactions resulted in somewhat smaller utility shifts that were in the expected directions (+0.006 and -0.011, respectively). SG utility of current health (mean = 0.897) demonstrated construct validity through statistically significant correlations with patient-reported outcome measures. DISCUSSION: The three injection attributes were associated with small utility shifts in the expected directions. Dose frequency appears to be the most important of the three attributes from the patients' perspective. The vignette-based SG approach was feasible and useful for assessing added utility or disutility of injection-related attributes associated with treatments for type 2 diabetes.