Time Trade-Off Utilities for Hereditary Angioedema Health and Caregiver States.

BACKGROUND: Hereditary angioedema (HAE) is an inherited chronic rare disease characterised by recurrent swelling attacks that are associated with significant physical and psychological burden. There is limited understanding of the effect of attack location on this burden and of caregiver burden. OBJECTIVE: Our objective was to capture the relative burden of HAE health and caregiver states, including different attack locations, through a time trade-off (TTO) analysis involving participants from the general public. METHODS: Qualitative interviews were undertaken to inform vignette development for the TTO study, including vignettes for abdominal, facial, hand and laryngeal attack health states, and an attack-free and caregiver state. Members of the general public in England rated vignettes in TTO interviews, which included a visual analogue scale (VAS) component. For the development of the health state vignettes, qualitative interviews with 15 patients, 5 caregivers and 1 clinical expert were performed. TTO analysis was based on vignette valuation completed by 100 members of the general public. RESULTS: The TTO values were as follows: attack-free, 0.783 (standard deviation [SD] 0.316); hand: 0.582 (SD 0.380); facial: 0.483 (SD 0.448); abdominal: 0.345 (SD 0.458); and laryngeal: 0.128 (SD 0.529). The caregiver rating was 0.762 (SD 0.303). V' scores were similar and consistent with TTO values. CONCLUSION: TTO utility values demonstrate that HAE places a significant burden on patients, which is influenced by attack location, and on caregivers. These utility weights can provide important information on quality of life for future economic evaluations of treatments.

Development of the neurotrophic keratopathy questionnaire: qualitative research.

BACKGROUND: Neurotrophic keratopathy/keratitis (NK) is a rare disease of the cornea that can lead to anatomical loss of the eye. Little is known about the NK experience from the patients' perspective. The objectives of this study were to examine the symptomatic experience and impacts of NK on patients and assess the overall comprehension, relevance, and content validity of a new questionnaire. METHODS: This was a cross-sectional, qualitative study conducted with NK patients with varying levels of disease severity, recruited from one clinical site. One-on-one interviews using concept elicitation and cognitive interviewing techniques were conducted. RESULTS: Fourteen NK patients participated; 64.3% were female (n = 9), mean age was 65.7 ± 13.3, and 14.3% (n = 2), 21.4% (n = 3), and 64.3% (n = 9) were classified as Mackie stage I, stage II, or stage III, respectively. Participants reported 24 concepts, including: redness (n = 12, 86%), sensitivity to light (n = 11, 79%), general discomfort (n = 9, 64%), dry eye (n = 9, 64%), reduced visual acuity (n = 9, 64%), blurred vision (n = 8, 57%), and eye fatigue (n = 8, 57%). No new concepts were reported after the 13th interview. The most frequently reported impacts included frustration (n = 10, 71%), driving impairment (n = 8, 57%), reading impairment (n = 7, 50%), difficulty watching television (n = 7, 50%), and concern with potentially losing their eyesight due to NK (n = 6, 43%). Participants provided positive feedback on the draft NK Questionnaire (NKQ) and felt that it was comprehensive and relevant to their experience with NK. Additionally, the recall period, instructions, item concepts, and response options were well-understood by participants. Minor revisions were made to the tool for consistency (i.e., the timeframe "in the past 7 days" was added to items 12-14); item 14 was modified to include "how often"; examples were added to item 9. CONCLUSIONS: The results of the concept elicitation portion of the qualitative study support the content validity of the draft NKQ. The clinically significant concepts identified in the literature and raised during concept elicitation are included as items in the questionnaire. Further assessment of the psychometric properties should be conducted in support of this new tool to measure the effect of new treatments on symptoms and impacts associated with NK.

Measurement properties of the Short Form-36 (SF-36) and the Functional Assessment of Cancer Therapy - Anemia (FACT-An) in patients with anemia associated with chronic kidney disease.

BACKGROUND: Anemia is a common and debilitating manifestation of chronic kidney disease (CKD). Data from two clinical trials in patients with anemia of CKD were used to assess the measurement properties of the Medical Outcomes Survey Short Form-36 version 2 (hereafter SF-36) and the Functional Assessment of Cancer Therapy-Anemia (FACT-An). The Vitality and Physical functioning domains of the SF-36 and the FACT-An Total, Fatigue and Anemia subscales were identified as domains relevant to CKD-associated anemia. METHODS: A total of 204 patients aged 18-80 years were included in the analyses that included internal consistency (Cronbach's alpha), test-retest reliability (intraclass correlation coefficients [ICCs]), convergent and known-groups validity, responsiveness, and estimates of important change. RESULTS: Both the SF-36 and the FACT-An had strong psychometric properties with high internal consistency (Cronbach's alpha: 0.69-0.93 and 0.79-0.95), and test-retest reliability (ICCs: 0.64-0.83 and 0.72-0.88). Convergent validity, measured by correlation coefficients between similar concepts in SF-36 and FACT-An, ranged from 0.52 to 0.77. Correlations with hemoglobin (Hb) levels were modest at baseline; by Week 9, the correlations with Hb were somewhat higher, r = 0.23 (p < 0.05) for SF-36 Vitality, r = 0.22 (p < 0.05) for FACT-An Total, r = 0.26 (p < 0.001) for FACT-Fatigue and r = 0.22 (p < 0.01) for Anemia. Correlations with Hb at Week 13/17 were r = 0.28 (p < 0.001) for SF-36 Vitality and r = 0.25 (p < 0.05) for Role Physical; FACT-An Total correlation was r = 0.33 (p < 0.0001), Anemia was r = 0.28 (p < 0.001), and Fatigue was r = 0.30 (p < 0.001). The SF-36 domains and Component Summary scores (p < 0.05-p < 0.0001) demonstrated ability to detect change. For the FACT-An, significant differences (p < 0.05-p < 0.0001) were observed between responder and non-responder change scores: important change score estimates ranged from 2 to 4 for Vitality and 2-3 for Physical functioning. Important change scores were also estimated for the FACT-An Total score (6-9), the Anemia (3-5), and Fatigue subscale (2-4). CONCLUSIONS: Both the SF-36 Vitality and Physical function scales and the FACT-An Total, Fatigue and Anemia scales, are reliable and valid measures for assessing health-related quality of life in anemia associated with CKD.

Neuropathic pain: A patient-centred approach to measuring outcomes.

BACKGROUND: Neuropathic pain (NP) is a complex, chronic pain state initiated by a primary lesion or dysfunction of the nervous system and presents as a variety of symptoms across multiple disease states. OBJECTIVE: To develop a patient-centred conceptual model of symptoms and impacts in subjects with diabetic peripheral neuropathy (DPN) or post-herpetic neuralgia (PHN) that can inform the measurement strategy in clinical trials. METHOD: Thirty subjects with DPN or PHN participated in in-person interviews which were performed until saturation was achieved. Transcripts were analysed in ATLAS.ti. RESULTS: Interviews were completed with DPN subjects (United States, n = 10; Japan, n = 10) and PHN subjects (United States, n = 5; Japan, n = 5). Numbness and tingling were frequently reported symptoms in the DPN population while itchiness and hypersensitivity were predominant in PHN. Both populations experienced burning and ache/soreness with similar frequency. DPN subjects experienced pain primarily in their lower extremity (eg feet, ankles), while PHN subjects experienced pain primarily in the chest and back. Impacts reported by DPN subjects included difficulty walking, sleep disturbance and climbing stairs. Impacts in PHN subjects included sleep disturbance, avoidance of physical contact, being angry/frustrated and being sad/depressed. Overall, concepts in Japan were not qualitatively different from the United States. Conceptual models of NP were generated based on the concepts elicited. CONCLUSIONS: This research highlights core concepts to measure from the patient's perspective. Moreover, it enables the assessment of existing measures, the possible modification of these measures, or if a new NP measure with improved sensitivity and responsiveness is merited.

Development and content validation of a patient-reported endometriosis pain daily diary.

BACKGROUND: Endometriosis is a common gynecological disorder that causes inflammation and pelvic pain. Endometriosis-related pain is best captured with patient-reported outcome (PRO) measures, however, assessment of endometriosis-related pain in clinical trials has been difficult in the absence of a reliable and valid PRO instrument. We describe the development of the Endometriosis Pain Daily Diary (EPDD), an electronic PRO developed as a survey instrument to assess endometriosis-related pain and its impact on patients' lives. METHODS: The EPDD was initially developed on the basis of an existing Endometriosis Pain and Bleeding Diary, a targeted review of relevant literature, clinical expert interviews, and open-ended (concept elicitation) patient interviews in the United States (US) and Japan which captured patients' experience with endometriosis. Cognitive interviews of patients with endometriosis were conducted to evaluate patient comprehension of the EPDD items. A conceptual model of endometriosis was developed, and meetings with US and European regulatory authorities provided feedback for validating the EPDD in the context of clinical trials. Translatability assessments of the EPDD were conducted to confirm its appropriate interpretation and ease of completion across 17 languages. RESULTS: The iterative development progressed through three versions of the instrument. The EPDDv1 included 18 items relating to dysmenorrhea/pelvic pain, dyspareunia and sexual activity, bleeding, hot flashes, daily activities, and use of rescue medication. The EPDDv2 was a larger 43-item survey tested in cognitive interviews and subsequently revised to yield the current 11-item EPDDv3, consisting of five core items relating to dysmenorrhea, non-menstrual pelvic pain, and dyspareunia, and six extension items relating to sexual activity, daily activities, and use of rescue medication. CONCLUSIONS: The EPDD is a PRO for the evaluation of endometriosis-related pain and its associated impacts on patients' lives. The EPDD represents an important step in providing a PRO that is relevant to patients with endometriosis-related pain in the context of a clinical study setting (ie, fit-for-purpose), designed to evaluate pain associated with endometriosis, including regulatory agency support for its further exploration in clinical trials.

Health-Related Quality of Life of Patients with Acute Myeloid Leukemia: A Systematic Literature Review.

INTRODUCTION: Patients with acute myeloid leukemia (AML), especially those with relapsed or refractory AML, have poor clinical prognosis and outcomes. Health-related quality of life (HRQoL) assessments have become increasingly important in oncology, aiding in identifying and informing supportive therapy needs during treatment and beyond; however, HRQoL in hematology, and AML in particular, has received relatively minor attention. The aim was to identify and summarize estimates of HRQoL in patients with AML, including patients with relapsed or refractory AML. METHODS: A systematic literature review was performed. MEDLINE and EMBASE databases were searched for peer-reviewed literature published between 2004 and 2014 in the US and Europe. Abstracts from four relevant conference proceedings between 2012 and 2014 were reviewed. Data from eligible studies were extracted describing the HRQoL instruments used, domains assessed, and HRQoL scores reported. RESULTS: Fourteen peer-reviewed studies met the eligibility criteria and were included in the review. Cancer- or leukemia-specific HRQoL measures were used in 78.6% of the studies. Overall, HRQoL was superior among AML survivors compared to individuals on active treatment. Fatigue was identified as the most problematic symptom domain in patients, irrespective of their treatment status. Reported HRQoL declined shortly after diagnosis or treatment initiation and recovered over time. CONCLUSION: The included studies identified a decrease in HRQoL after treatment initiation and highlighted the role of fatigue in HRQoL in this patient population. Limited HRQoL data were identified among relapsed or refractory AML patients although they have worse prognostic outcomes. New treatment options that have less negative impact on HRQoL or health initiatives specifically targeting HRQoL of patients with AML are warranted. In addition, further studies exploring HRQoL in the relapsed or refractory patient population are needed to inform disease management and treatment decisions.

Capsaicin 8% Patch Versus Oral Neuropathic Pain Medications for the Treatment of Painful Diabetic Peripheral Neuropathy: A Systematic Literature Review and Network Meta-analysis.

PURPOSE: A network meta-analysis (NMA) was performed, aiming to assess the relative efficacy and tolerability of the capsaicin 179-mg (8% weight for weight) cutaneous patch (capsaicin 8% patch) compared with oral, centrally acting agents (ie, pregabalin, gabapentin, duloxetine, amitriptyline) in patients with painful diabetic peripheral neuropathy (PDPN). METHODS: A systematic search of EMBASE/MEDLINE, Cochrane Library, and the National Health Service Centre for Reviews and Dissemination Database of Abstracts of Reviews of Effects was conducted to identify all randomized controlled trials. Data from eligible studies according to predefined inclusion and exclusion criteria were extracted, and analyses were based on aggregate-level data. Efficacy outcomes were the proportions of patients with ≥30% and ≥50% reductions in pain, and tolerability outcomes were somnolence, dizziness, nausea, diarrhea, constipation, headache, fatigue, insomnia, and rate of discontinuation due to adverse events (AEs). Data were analyzed by using a Bayesian NMA. Fixed and random effects models were estimated. Relative treatment effect was presented as odds ratios (ORs) with 95% CIs. Sources of heterogeneity were assessed. FINDINGS: The NMA included 25 randomized controlled trials. For ≥30% pain reduction, the capsaicin 8% patch was significantly more effective than placebo (OR, 2.28 [95% CI, 1.19-4.03]), exhibited a numerical advantage compared with pregabalin (OR, 1.83 [95% CI, 0.91-3.34]) and gabapentin (OR, 1.66 [95% CI, 0.74-3.23]), and had similar efficacy compared with duloxetine (OR, 0.99 [95% CI, 0.5-1.79]). The evidence available was not sufficient to assess the relative efficacy of amitriptyline. In the NMA for tolerability, the capsaicin 8% patch was only included for headache because the incidence was 0% for the other outcomes. Oral, centrally acting agents had a significantly elevated risk compared with placebo for somnolence (pregabalin, gabapentin, duloxetine, and amitriptyline), dizziness (pregabalin, gabapentin, duloxetine, and amitriptyline), nausea (duloxetine), diarrhea (duloxetine), fatigue (duloxetine), and discontinuation because of AEs (pregabalin, gabapentin, and duloxetine). Compared with pregabalin and gabapentin, duloxetine had a significantly lower risk of dizziness but a significantly higher risk of nausea. IMPLICATIONS: This NMA suggests that the efficacy observed with the capsaicin 8% patch is similar to that observed with oral agents (ie, pregabalin, duloxetine, gabapentin) in patients with PDPN. The oral agents were associated with a significantly elevated risk of somnolence, dizziness, fatigue, and discontinuation because of AEs compared with placebo. The capsaicin 8% patch was as effective as oral centrally acting agents in these patients with PDPN but offers systemic tolerability benefits.

An exploration of differences between Japan and two European countries in the self-reporting and valuation of pain and discomfort on the EQ-5D.

PURPOSE: To investigate the systematic differences in the self-reporting and valuation of overall health and, in particular, pain/discomfort between three countries (England/UK, Japan, and Spain) on the EQ-5D. METHODS: Existing datasets were used to explore differences in responses on the EQ-5D descriptive system between Japan (3L and 5L), the UK (3L), England (5L), and Spain (5L), particularly on the dimension of pain/discomfort. The role of different EQ dimensions in determining self-reported overall health scores for the EuroQol visual analog scale (EQ-VAS) was investigated using ordinary least squares regression. Time trade-off (TTO) results from Japanese and UK respondents for the EQ-5D-3L as well as Japanese and English respondents for the EQ-5D-5L were compared using t tests. RESULTS: For the EQ-5D-3L, a higher percentage of respondents in Japan than in the UK reported 'no pain/discomfort' (81.6 vs 67.0%, respectively); for the EQ-5D-5L, the proportions were 79.2% in Spain, 73.2% in Japan, and 63-64% in England, after adjusting for age differences in samples. The 'pain/discomfort' dimension had the largest impact on respondents' self-reported EQ-VAS only for EQ-5D-3L in Japan. Using the EQ-5D-3L, Japanese respondents were considerably less willing to trade off time to avoid pain/discomfort than the UK respondents; for example, moving from health state, 11121 (some problems with pain/discomfort) to 11131 (extreme pain/discomfort) represented a decrement of 0.65 on the observed TTO value in the UK compared with 0.15 in Japan. Using the EQ-5D-5L, Japanese respondents were also less willing to trade off time to avoid pain/discomfort than respondents in England; however, the difference in values was much smaller than that observed using EQ-5D-3L data. CONCLUSIONS: This study provides evidence of between-country differences in the self-reporting and valuation of health, including pain/discomfort, when using EQ-5D in general population samples. The results suggest a need for caution when comparing or aggregating EQ-5D self-reported data in multi-country studies.

Evaluating the Measurement Properties of the Self-Assessment of Treatment Version II, Follow-Up Version, in Patients with Painful Diabetic Peripheral Neuropathy.

Background. The Self-Assessment of Treatment version II (SAT II) measures treatment-related improvements in pain and impacts and impressions of treatment in neuropathic pain patients. The measure has baseline and follow-up versions. This study assesses the measurement properties of the SAT II. Methods. Data from 369 painful diabetic peripheral neuropathy (PDPN) patients from a phase III trial assessing capsaicin 8% patch (Qutenza®) efficacy and safety were used in these analyses. Reliability, convergent validity, known-groups validity, and responsiveness (using the Brief Pain Inventory-Diabetic Neuropathy [BPI-DN] and Patient Global Impression of Change [PGIC]) analyses were conducted, and minimally important differences (MID) were estimated. Results. Exploratory factor analysis supported a one-factor solution for the six impact items. The SAT II has good internal consistency (Cronbach's alpha: 0.96) and test-retest reliability (intraclass correlation coefficients: 0.62-0.88). Assessment of convergent validity showed moderate to strong correlations with change in other study endpoints. Scores varied significantly by level of pain intensity and sleep interference (p < 0.05) defined by the BPI-DN. Responsiveness was shown based on the PGIC. MID estimates ranged from 1.2 to 2.4 (pain improvement) and 1.0 to 2.0 (impact scores). Conclusions. The SAT II is a reliable and valid measure for assessing treatment improvement in PDPN patients.

Cross-sectional survey in CKD patients across Europe describing the association between quality of life and anaemia.

BACKGROUND: Deteriorating renal function in chronic kidney disease (CKD) patients is commonly associated with reduced haemoglobin levels, adding to the already considerable humanistic burden of CKD. This analysis evaluated the impact of anaemia on disease burden in patients with CKD stages 3-4, and in those on dialysis. METHODS: This was a descriptive, cross-sectional analysis of European data from an Adelphi CKD Disease-Specific Programme. This programme collected data from patients and their treating nephrologists/endocrinologists; patient- and physician-reported data were matched for each patient. Health-related quality of life (HRQoL) data were obtained through patient completion of the EQ-5D, SF-12 and KDQOL-36. Additional information was obtained via physician reporting of patient symptoms, and patients' reports of impaired activity. Anaemia was defined by haemoglobin level and/or current use of erythropoiesis stimulating agents. RESULTS: Significant, but modest Spearman's rank correlations were observed between haemoglobin levels and extent of HRQoL impairment, regardless of instrument used (range 0.19-0.23; all P-values < 0.0001). When stratified by anaemia status, impairment was consistently lower for anaemic than non-anaemic CKD patients across measurement scales (e.g. EQ-5D index value [standard deviation {SD}] 0.72 [0.31] vs 0.83 [0.23], respectively; P < 0.0001). Physician-reported patient tiredness was associated with increased disease burden at all levels of CKD studied (total EQ-5D index value [SD] in patients reporting no tiredness vs tiredness 0.81 [0.26] vs 0.70 [0.30] respectively; P < 0.0001) with P < 0.0001 for no tiredness vs tiredness at all stages of CKD. The presence of anaemia was associated with impaired activity levels at CKD stages 3 (37.5 % vs 28.4 %, respectively; P = 0.0044) and 4 (48.1 % vs 39.9 %, respectively; P = 0.0292), and in patients on dialysis (52.0 % vs 45.0 %, respectively; P = 0.0732). CONCLUSIONS: The analysis found that CKD patients with anaemia typically had a lower HRQoL than those without anaemia. The impairment correlated with anaemia was more apparent in non-dialysis patients with CKD stages 3 or 4 than in those receiving dialysis. Coexisting CKD and anaemia may have an impact on patient HRQoL similar to other chronic conditions such as diabetes, epilepsy or certain forms of cancer.

The Patient Perspective on Living with Acute Myeloid Leukemia.

INTRODUCTION: Acute myeloid leukemia (AML) imposes significant burden on patients, their families, and the healthcare system. Published literature has reported many AML signs and symptoms, as well as their impact on patients. However, there are no publications on the experience of living with AML from the patient's perspective. In this study, we performed qualitative interviews with patients with AML to understand their experience. METHODS: Participants were recruited from the US and Japan. All patients were screened to assess eligibility, and were divided into four subgroups (i.e., newly-diagnosed, high-intensity chemotherapy; newly-diagnosed, low-intensity chemotherapy; relapse/refractory; and post-transplant). Patients were interviewed over the phone by a trained researcher and asked about their day-to-day experience with AML. Signs/symptoms and impacts were coded, analyzed using Atlas.ti software, and reported as frequencies, with the medians of patient-reported disturbance levels (0-10) computed for each symptom and impact. RESULTS: The most commonly reported sign/symptom in the US was fatigue (95.7%), followed by bruising and weakness (both 78.3%), and in Japan, nausea (94.4%), followed by fatigue and headache (both 88.9%). The most commonly reported impact in the US was a decreased ability to maintain social/familial roles (91.3%), followed by anxiety and a decreased ability to function (both 87.0%), and most commonly reported in Japan was anxiety, a decreased ability to function, and remission uncertainty (94.4%). CONCLUSION: Although the frequency of signs/symptoms and their level of disturbance varied between the US and Japan, there was remarkable consistency in the types of signs/symptoms and impacts reported across all patients. The consistency in the experience of the disease across patients suggests that measurement of AML experience can be achieved by using the same tool for most, if not all, of these patients. FUNDING: Astellas Pharma Inc., Northbrook, IL, USA.

Humanistic and economic burden of painful diabetic peripheral neuropathy in Europe: A review of the literature.

AIMS: Painful diabetic peripheral neuropathy (PDPN) is a common complication of diabetes mellitus. A systematic literature review was conducted to provide an overview of published literature in the last 10-years on the epidemiology, humanistic burden and economic burden of PDPN in Europe. METHODS: A search was performed according to pre-defined strategy and review criteria in Embase, Pubmed, and conference proceedings databases from 2003 till December 2012. In total, 30 publications written in English covering the relevant patient population and topics of interest. RESULTS: European prevalence ranges from 6% to 34% in diabetes mellitus patients. PDPN has a significant humanistic and economic impact. Patients are limited in their general functioning and their ability to sleep and often experience anxiety and depression. Not surprisingly, PDPN is associated with reduced Health-Related-Quality-of-Life (HRQoL). PDPN patients incur high health care costs due to hospitalizations and outpatient visits. In addition, the painful symptoms cause impaired work productivity. Studies suggest both humanistic and economic burden increase with higher pain severity. CONCLUSIONS: The burden from PDPN appears to be higher with increasing pain severity. More severe pain leads to a higher impairment in daily functioning, sleep and HRQoL. Higher pain intensity also leads to increasing healthcare costs and work productivity losses.

Use of relative effectiveness information in reimbursement and pricing decisions in Europe.

Although comparative effectiveness has received considerable attention recently - especially in the USA - it is not a new concept. In Europe, it has been applied for some time now in the pricing and reimbursement processes of many countries. Each one uses it in its own way, however, with variations in the precise definition and the role it plays in the process. It remains to be seen whether the implementation of comparative effectiveness becomes more harmonized and whether it will be integrated better with the registration process. Regardless of the extent to which it is standardized, obtaining the data will remain a substantial hurdle, both methodologically and operationally. Everyone wants comparative effectiveness information but no one knows quite how to make it happen.

Cost-effectiveness of omalizumab for uncontrolled allergic asthma in the Netherlands.

BACKGROUND: Omalizumab, licensed for patients with uncontrolled persistent allergic (IgE mediated) asthma, was found to be cost-effective based upon its clinical trial data. Observational studies have been undertaken to determine the real life outcomes of using omalizumab in the community. OBJECTIVE: To determine the cost-effectiveness of omalizumab based upon observational data from the Netherlands and compare to its cost-effectiveness using clinical trial data. METHODS: An observational study (eXpeRience) recruited allergic asthma patients eligible for Omalizumab therapy and followed them while on treatment. At 1 year, data from the Dutch patients enrolled in eXpeRience were examined to estimate the number of exacerbations and resource use while on omalizumab therapy compared to the year prior to omalizumab use. Observational data were used in a Markov model to calculate the lifetime cost-effectiveness ratios. RESULTS: In the 1 year prior to omalizumab therapy the per-person rate of exacerbations was 3.39 compared to 1.07 in the year taking omalizumab. The discounted incremental lifetime additional costs for omalizumab were €55,865 for 1.46 additional quality-adjusted life years (QALY), resulting in €38,371/QALY. Using the INNOVATE clinical trial outcomes and current resource use, the prior ratio was €34,911/QALY, similar to the observational ratio. As in all observational studies, the main limitation is obtaining complete and accurate data. Patients with missing exacerbation or response data were excluded from this analysis. CONCLUSION: Non-clinical trial experience with omalizumab supported the finding of fewer exacerbations in the allergic asthma population while treated with omalizumab, and therapy was found to continue to have an attractive cost-effectiveness ratio.

Health economics and outcomes research within drug development: challenges and opportunities for reimbursement and market access within biopharma research.

Healthcare decision makers who determine funding for new medical technologies depend on manufacturers to provide evidence of the technology's efficacy, safety and cost-effectiveness. Constrained budgets and increasing reliance on formal health technology assessment (HTA) have created an abundance of external hurdles that manufacturers must navigate to ensure successful product commercialization. These demands have pushed pharmaceutical companies to adjust their internal structures to coordinate generation of appropriate evidence. In this article we summarize internal and external opportunities for manufacturers to establish a foundation of evidence for successful market access, starting in Phase I of development and continuing throughout the post-approval product lifecycle.

Utility estimation in chronic obstructive pulmonary disease: a preference for change?

Economic evaluations of chronic obstructive pulmonary disease (COPD) incorporate utilities through multi-attribute utility (MAU) measures, most commonly the EQ-5D, to report health-related quality-of-life (HR-QOL) changes or differences. Questions have been raised about the sensitivity of these measures in COPD. Limitations in detecting adequate patient-level changes in HR-QOL over time in stable and exacerbation states compared with disease-specific instruments could also result in underestimation of known treatment benefits. The purpose of this article was to present and discuss the empirical evidence on the validity of generic MAU measures within the COPD population. We built upon a previously conducted validation review for the period 1997-2007 that used 'respiratory disease' and 'EQ-5D' as keywords. For this discussion, PubMed and EMBASE databases were searched for articles in English from 1988 to August 2009, using similar search words. Based on the performance of MAU measures in COPD and exacerbations, they appear to have limited discriminatory ability, particularly between moderate and severe COPD, despite known differences in HR-QOL. Sensitivity to clinically relevant change in stable COPD over time due to treatment also appears limited. Current research suggests adequate sensitivity regarding detecting the onset and resolution of an exacerbation; however, sensitivity is limited in the short term, such as daily changes in health status. The evidence suggests responsiveness of MAU measures may be restricted to large within-patient change, which leads to difficulties in evaluating the subtle but important impact of exacerbations. Studies presenting alternative methods of deriving COPD-related utilities are also discussed. Overall, the insensitivities of generic MAU measures in COPD can lead to biased cost-effectiveness analyses and ill-informed economic decisions. Alternative measures such as condition-specific preference-based measures may be used in circumstances where more sensitivity is needed. The trade-off allows relevant and sensitive matters most important to patients to be evaluated; however inevitable gaps such as those related to adverse events are not considered.

Burden of illness for patients with non-dialysis chronic kidney disease and anemia in the United States: review of the literature.

OBJECTIVE: To assess the health-related quality of life (HRQL) and economic burden of chronic kidney disease (CKD) related anemia in non-dialysis patients in the United States (US) via literature review. METHODS: MEDLINE, EMBASE, PROQOLID, and Cochrane Library/Renal Group Resources were searched. Studies were appraised for patient populations, disease-specific versus generic HRQL assessments, and type and magnitude of health-related costs. RESULTS: The treatment costs for CKD patients with anemia compared to those without anemia were significantly higher and were blunted but persistent after controlling for comorbidities and confounders. Intervention with erythropoiesis stimulating agents (ESA) decreased anemia and avoided hospital admissions. Costs were higher when anemia was poorly controlled or untreated. HRQL burden was mainly due to physical limitations and difficulty in ability to perform activities of daily living. Significant positive correlations between increases in hemoglobin levels and HRQL measures were reported. CONCLUSIONS: Although evidence is limited, the economic and HRQL burden of non-dialysis CKD-related anemia is substantial. Under-treatment of anemia may contribute to higher resource consumption and higher costs; however, patient co-morbidities, use of erythropoietin-stimulating agents, and overall management introduce potential confounds. The contribution of anemia to humanistic disease burden is due to a constellation of factors, including physical activity and functional status.

Systemic impairment in relation to disease burden in patients with moderate COPD eligible for a lifestyle program. Findings from the INTERCOM trial.

INTRODUCTION: In contrast with the frequency distribution of chronic obstructive pulmonary disease (COPD) stages in the population, in which the majority of the patients is classified as GOLD 2, much less information is available on the prevalence and implications of systemic manifestations in less severe patients relative to GOLD 3 and 4. AIM: To characterize local and systemic impairment in relation to disease burden in a group of GOLD 2 COPD patients (n = 127, forced expiratory volume in one second (SD): 67 (11)% pred) that were eligible for the Interdisciplinary Community-based COPD management (INTERCOM) trial. METHODS: Patients were included for this lifestyle program based on a peak exercise capacity (Wmax) < 70% of predicted. Metabolic and ventilatory response to incremental cycle ergometry, 6 minute walking distance (6MWD), constant work rate test (CWR), lung function, maximal inspiratory pressure (Pimax), quadriceps force (QF), quadriceps average power (QP) (isokinetic dynamometry), handgrip force (HGF) and body composition were measured. Quality of life (QoL) was assessed by the St. George's Respiratory Questionnaire (SGRQ) and dyspnea by the modified Medical Research Council (MRC) dyspnea scale. Exacerbations and COPD-associated hospital admissions in 12 months prior to the start of the study were recorded. Burden of disease was defined in terms of exercise capacity, QoL, hospitalization, and exacerbation frequency. GOLD 2 patients were compared with reference values and with GOLD 3 patients who were also included in the trial. RESULTS: HGF (77.7 (18.8) % pred) and Pimax (67.1 (22.5)% pred) were impaired in GOLD 2, while QF (93.5 (22.5)% pred) was only modestly decreased. Depletion of FFM was present in 15% of weight stable GOLD 2 patients while only 2% had experienced recent involuntary weight loss. In contrast to Wmax, submaximal exercise capacity, muscle function, and body composition were not significantly different between GOLD 2 and 3 subgroups. Body mass index and fat-free mass index were significantly lower in smokers compared to ex-smokers. In multivariate analysis, QF and diffusing capacity (DLco) were independently associated with Wmax and 6 MWD in GOLD 2 while only 6 MWD was identified as an independent determinant of health-related QoL. HGF was an independent predictor of hospitalization. CONCLUSIONS: This study shows that also in patients with moderate COPD, eligible for a lifestyle program based on a decreased exercise capacity, systemic impairment is an important determinant of disease burden and that smoking affects body composition.

A 1-year prospective cost-effectiveness analysis of roflumilast for the treatment of patients with severe chronic obstructive pulmonary disease.

RATIONALE: Roflumilast is an oral, once-daily phosphodiesterase IV (PDE4) inhibitor under investigation for chronic obstructive pulmonary disease (COPD). This study investigated the cost effectiveness of roflumilast in patients with severe to very severe COPD from the perspective of the UK society and UK NHS. METHODS: The analysis was conducted alongside a 1-year, randomised, double-blind, placebo-controlled, multinational trial. The trial included 1514 COPD patients aged >or=40 years with a post-bronchodilator forced expiratory volume in 1 second (FEV1) % predicted