The burden of allergic rhinitis and allergic rhinoconjunctivitis on adolescents: A literature review.

OBJECTIVE: To evaluate the literature regarding the burden of allergic rhinitis (AR) and allergic rhinoconjunctivitis (ARC) in adolescents (aged 10-19 years). DATA SOURCES: Searches were performed in MEDLINE, Embase, Health Technology Assessment Database, and National Health Service Economic Evaluation Database for studies that evaluated concepts of symptoms, quality of life (QOL), daily activities, sleep, examination performance, school absenteeism and presenteeism, and treatment burden in adolescents with AR or ARC. STUDY SELECTIONS: English-language journal articles indexed in the last 15 years describing noninterventional, population-based studies. Records were assessed by 2 independent reviewers. RESULTS: A total of 27 articles were identified; outcomes evaluated were symptoms (n = 6 studies), QOL (n = 9), daily activities (n = 5), emotional aspects (n = 3), sleep (n = 6), education (n = 7), and treatment burden (n = 2). AR symptoms rated most bothersome were rhinorrhea, nasal congestion, and itchy eyes. QOL was worse in adolescents with AR vs controls regardless of QOL instrument used. Nasal symptoms and nasal obstruction were more likely to be associated with poor QOL in adolescents than in adults or younger children, respectively. Daily functioning and sleep were also negatively affected by AR. In addition, a detrimental effect on absenteeism, school productivity, and academic performance was reported. CONCLUSION: Although AR and ARC are sometimes perceived as trivial conditions, this review indicates that their effect on adolescent life is negative and far-reaching. It is critical that clinicians gain a greater understanding of the unique burden of AR and ARC in adolescents to ensure they receive prompt and appropriate care and treatment to improve clinical and academic outcomes.

Treatment-Related Attributes of Diabetes Therapies and How People with Type 2 Diabetes Report Their Impact on Indicators of Medication-Taking Behaviors.

Purpose: Understanding the treatment-related attributes influencing medication-taking behaviors in people with type 2 diabetes (T2D) is important for delivery of patient-centered care. This review aimed to identify and summarize studies in which people with T2D (PwD) directly indicated the treatment-related attributes associated with medication-taking behaviors or intentions. Materials and Methods: EMBASE and PubMed were searched for studies (Jan 2005-May 2021) reporting the link between PwD-expressed diabetes treatment-related attributes and the decision to initiate, adhere to, or discontinue a T2D medication. Eligible studies reported attributes associated with oral antidiabetes drugs or injectables (not insulin). Studies not explicitly exploring the link between attributes and indicators of behaviors (eg most discrete-choice experiments [DCE] and those interrogating electronic medical records or claims databases) were excluded, as were studies where the link between attribute and behavior came from anyone but the PwD. Results: Of the 6464 studies identified, 16 were included. Studies were conducted across multiple countries; the USA was most represented (n = 8 studies). The impact of treatment attributes was described on indicators of initiation (n = 3), adherence (n = 12), and discontinuation (n = 4). Some studies evaluated multiple behaviors. PwD perspectives were solicited by structured questionnaires (n = 10), qualitative approaches (n = 4), or DCE explicitly exploring the link to medication-taking behaviors (n = 2). Closed- (n = 9) and open-ended questions (n = 7) were employed. Across studies, several factors including glycemic efficacy (n = 9), weight change (n = 9), dosing frequency (n = 9), hypoglycemia (n = 8), gastrointestinal adverse events (n = 8), regimen complexity (n = 6), route of administration (n = 3), and cardiovascular risk (n = 1) were reported as influencing behaviors, being motivators or barriers to initiation, adherence, or discontinuation. Conclusion: Several attributes influence how PwD take their medications. Insights gained directly from PwD have the potential to assist stakeholders in making more informed, patient-centered, treatment decisions, thus choosing and managing medications that PwD are comfortable initiating and persisting with over the longer term.

Weight Change and the Association with Adherence and Persistence to Diabetes Therapy: A Narrative Review.

PURPOSE: Type 2 diabetes (T2D) medication adherence is poor and is impacted by individual drug characteristics. Treatment-associated weight change can affect medication-taking behavior. This review aimed to explore weight change on T2D therapy and consider its impact on adherence and discontinuation. METHODS: Searches were conducted in MEDLINE and EMBASE (2005 to September 2020), and among recent congress abstract books for studies providing data on medication adherence or discontinuation and weight change in people with T2D (PwD). RESULTS: Nine studies meeting the inclusion criteria were identified from 9188 bibliographic records. All three studies exploring weight change and discontinuation reported weight loss to be associated with higher persistence. Seven studies of varying design explored weight change and adherence. Four reported absolute weight change (kg) and adherence: one pooled data from different diabetes medications and demonstrated that self-reported adherence was significantly associated with weight loss; however, three studies found that weight change in adherent PwD was in the direction of the known weight profile (loss/gain) of the evaluated drug. Categorical weight loss (≥3%) and adherence were reported in two studies: one reported that numerically more adherent versus non-adherent PwD lost ≥3% weight regardless of the drug's weight profile, the other showed that early weight loss with a glucagon-like peptide-1 agonist was significantly associated with better adherence. One study reported adherence by categorical weight change; as weight loss increased, adherence scores improved, regardless of drug type. CONCLUSION: Findings suggest that discontinuation rates may be lower in PwD who lose as compared to those who gain weight on T2D treatment. The evidence base on adherence and weight change is more challenging to interpret due to the range of study designs. Given the importance of weight control in T2D, further research exploring the individual's treatment, weight journey, and behaviors over time should be undertaken.

Missed and Mistimed Insulin Doses in People with Diabetes: A Systematic Literature Review.

Background: Development of coordinated management approaches is important to facilitate self-care in people with diabetes (PwD). Gaining a better understanding of suboptimal insulin use is key in this endeavor. This review aimed, for the first time, to systematically identify and narratively summarize real-world evidence on the extent of suboptimal insulin use (missed and mistimed insulin) in PwD. Methods: A systematic literature search of MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews identified studies reporting on missed and mistimed insulin dosing. Results: From 3305 studies, 37 publications reporting on 30 unique studies that involved 58,617 PwD were included. Studies were conducted across 12 different countries and most employed cross-sectional surveys. Observations regarding missed and mistimed insulin doses were reported in 25 and 10 studies, respectively. PwD reported missing insulin doses, but rates varied due to differences in reporting methods, participant populations, and insulin regimens. The association between missed dosing and glycemic control was evaluated in ten studies in which the authors reported lower glycated hemoglobin (HbA1c) levels in PwD who did not omit insulin. The proportion of PwD reporting mistiming of insulin was in the range of 20-45%, depending on the study; this was associated with higher rates of hypoglycemia and higher HbA1c as reported by study authors. Reasons for suboptimal insulin use were multifactorial, occurring due to disrupted daily routines, social situations, and hypoglycemia avoidance. Conclusions: This review suggests that suboptimal insulin use is widespread and that PwD using insulin may still be struggling with disease management. There is an unmet need for better integrated support in managing the complexities of insulin therapy and for the development of systems (e.g. digital solutions) that empower people to take control of insulin-treated diabetes.

Clinical outcomes associated with anti-obesity medications in real-world practice: A systematic literature review.

Anti-obesity medications (AOMs) are efficacious and well tolerated in randomized controlled trials, but findings may not be generalizable to routine clinical practice. This systematic literature review aimed to identify real-world (RW) evidence for AOMs to treat adults ( ≥ 18 years) with obesity or overweight (BMI  ≥  27 kg/m2 ). Searches conducted in MEDLINE, Embase, Health Technology Assessment (HTA) Database, National Health Service (NHS) Economic Evaluation Database, and Cochrane Central Register of Controlled Trials for studies of relevant FDA-approved AOMs yielded 41 publications. Weight loss (WL) was consistently observed, with 14% to 58.6% of patients achieving ≥ 5% WL on orlistat, phentermine/topiramate, naltrexone/bupropion, phentermine, or liraglutide in studies of 3-6 months' duration where this was measured. When cardiometabolic risk factors were assessed, AOMs reduced or had no impact on blood pressure, lipids, or glycemia. RW data on the impact of AOMs on existing obesity-related comorbidities and mortality were generally lacking. AOMs were associated with various adverse events, but these were of mild to moderate severity and no unexpected safety signals were reported. A pattern of poor adherence and persistence with AOMs was observed across studies. Overall, the review confirmed the effectiveness of AOMs in RW settings but demonstrated large gaps in the evidence base.

Real-World Effectiveness of Dulaglutide in Patients with Type 2 Diabetes Mellitus: A Literature Review.

INTRODUCTION: Randomized controlled trials (RCTs) have demonstrated the efficacy of dulaglutide in adults with type 2 diabetes mellitus (T2DM), but results may not be generalizable in routine practice. This pragmatic literature review aimed to summarize real-world evidence (RWE) for dulaglutide. METHODS: The MEDLINE, EMBASE, NHS Economic Evaluation Database, and Health Technology Assessment databases were searched from January 2014 to July 2019 for studies providing RWE for dulaglutide in adults with T2DM regarding at least one outcome of interest (change in glycated hemoglobin [HbA1c]; weight; adherence; persistence; discontinuation; costs; healthcare resource utilization; health-related quality of life; patient satisfaction; and preference). Relevant congress abstracts were identified from EMBASE. RESULTS: A total of 29 studies (11 articles; 18 abstracts) were included. RWE for dulaglutide was not identified for all outcomes of interest. Dulaglutide reduced HbA1c from baseline to 3-24 months by 0.5-2.2% across studies (n = 20), and 23.4-55.7% of patients achieved HbA1c < 7.0%. Weight was reduced by 2.1-6.4 kg across studies of 3-12 months (n = 15). Based on outcomes from ten studies, 27.2-61.0% of dulaglutide patients were adherent. Mean persistence was 146-152 days and > 250 days in 6- and 12-month studies, respectively. Most studies reported discontinuation rates of 26.2-37.0%. Adherence and persistence were consistently reported to be greater in dulaglutide-treated patients in RW settings compared with other glucagon-like peptide-1 receptor agonists. Dulaglutide was associated with lower costs per 1% reduction in HbA1c compared with exenatide, liraglutide, or basal insulin (n = 3 studies). CONCLUSION: Evidence from RWE studies suggests that dulaglutide may be associated with clinically relevant reductions in HbA1c, with a favorable adherence, persistence, and discontinuation profile in patients with T2DM in routine clinical practice. These findings provide additional insights regarding the potential value of dulaglutide in real-world settings that may assist healthcare decision makers in the delivery of patient-centered care.

Which multi-attribute utility instruments are recommended for use in cost-utility analysis? A review of national health technology assessment (HTA) guidelines.

BACKGROUND: Several multi-attribute utility instruments (MAUIs) are available from which utilities can be derived for use in cost-utility analysis (CUA). This study provides a review of recommendations from national health technology assessment (HTA) agencies regarding the choice of MAUIs. METHODS: A list was compiled of HTA agencies that provide or refer to published official pharmacoeconomic (PE) guidelines for pricing, reimbursement or market access. The guidelines were reviewed for recommendations on the indirect calculation of utilities and categorized as: a preference for a specific MAUI; providing no MAUI preference, but providing examples of suitable MAUIs and/or recommending the use of national value sets; and recommending CUA, but not providing examples of MAUIs. RESULTS: Thirty-four PE guidelines were included for review. MAUIs named for use in CUA: EQ-5D (n = 29 guidelines), the SF-6D (n = 11), HUI (n = 10), QWB (n = 3), AQoL (n = 2), CHU9D (n = 1). EQ-5D was a preferred MAUI in 15 guidelines. Alongside the EQ-5D, the HUI was a preferred MAUI in one guideline, with DALY disability weights mentioned in another. Fourteen guidelines expressed no preference for a specific MAUI, but provided examples: EQ-5D (n = 14), SF-6D (n = 11), HUI (n = 9), QWB (n = 3), AQoL (n = 2), CHU9D (n = 1). Of those that did not specify a particular MAUI, 12 preferred calculating utilities using national preference weights. CONCLUSIONS: The EQ-5D, HUI, and SF-6D were the three MAUIs most frequently mentioned in guidelines. The most commonly cited MAUI (in 85% of PE guidelines) was EQ-5D, either as a preferred MAUI or as an example of a suitable MAUI for use in CUA in HTA.

Patient preferences for glucagon-like peptide 1 receptor-agonist treatment attributes.

PURPOSE: The importance of patient-centered care in the management of type 2 diabetes mellitus (T2DM) is widely advocated. Understanding the attributes of T2DM medications important to patients is thus essential for effective management, in order to limit disease progression. This literature review aimed to identify studies comparing patient preferences, based on process and outcome attributes, between GLP1-receptor agonist (RA) profiles and between GLP1 RA and insulin profiles. METHODS: MEDLINE, Embase, PsycINFO, and the Cochrane Library (2005-present) were searched for studies in patients with T2DM or the general population that compared preferences for GLP1 RAs or GLP1 RAs versus insulin using contingent valuation, conjoint analysis (discrete-choice experiments [DCEs], willingness to pay), rating-based approaches of specific attributes, standard gamble, or time trade-off. Studies comparing drug A versus drug B without explicit attribute valuation were excluded. RESULTS: Ten records met eligibility criteria. Eight studies compared preferences for GLP1 RA- profile attributes, one compared GLP1 RA versus insulin glargine profiles, and one addressed both comparisons. Important attributes driving patient preferences in DCEs were dose frequency, type of device, needle size, change in glycated hemoglobin, and adverse-event profile. Time trade-off evaluations demonstrated that weekly GLP1 RA injection-device attributes (reconstitution, waiting during preparation, needle handling) had a measurable impact on preference. Willingness-to-pay analysis showed that patients were more willing to pay extra for attributes of once-daily liraglutide over twice-weekly exenatide or insulin. Direct preference elicitation in DCEs revealed that patients preferred medication profiles representing GLP1 RAs with less frequent dosing and preferred GLP1 RA profiles over insulin. CONCLUSION: Process and outcome attributes are important drivers of patient preference for GLP1 RAs. Findings from patient-preference studies can inform clinical decision-making and help align care with patient values, which has the potential to improve medication adherence and outcomes.

Cost of medication adherence and persistence in type 2 diabetes mellitus: a literature review.

PURPOSE: To explore published evidence on health care costs associated with adherence or persistence to antidiabetes medications in adults with type 2 diabetes mellitus (T2DM). METHODS: Primary research studies published between January 2006 and December 2015 on compliance, adherence, or persistence and treatment in patients with T2DM that document a link with health care costs were identified through literature searches in bibliographic databases and 2015 abstract books for relevant DM congresses. Results were assessed for relevance by two reviewers. The review was part of a larger overview evaluating the impact of adherence and persistence on a range of clinical and economic outcomes; only findings from the cost element are reported herein. RESULTS: A total of 4,662 de-duplicated abstracts were identified and 110 studies included in the wider review. Of these, 19 reported an association between adherence (n=13), persistence (n=5), or adherence and persistence (n=1), and health care costs. All studies were retrospective, with sample sizes ranging from 301 to 740,195. Medication possession ratio was the most commonly employed adherence measure (n=11). The majority of adherence studies (n=9) reported that medication adherence was associated with lower total health care costs. Pharmacy costs were often increased in adherent patients but this was offset by beneficial effects on other costs. Findings were more variable in persistence studies; three reported that higher pharmacy costs in persistent patients were not sufficiently offset by savings in other areas to result in a reduction in total health care costs. CONCLUSIONS: Few studies have evaluated the relationship between adherence, persistence, and health care costs in T2DM. However, it has been consistently shown that medication nonadherence increases health care costs, suggesting that cost savings from better adherence could be substantial. Available data support the economic case for identification of strategies that facilitate improved medication adherence in patients with T2DM.

Health-related quality of life burden of nonalcoholic steatohepatitis: a robust pragmatic literature review.

OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is a form of chronic liver disease (CLD): patients have an increased risk of developing cirrhosis, liver failure, and complications (e.g. hepatocellular carcinoma). NASH has a high clinical burden, and likely impairs patients' health-related quality of life (HRQoL), but there are currently no licensed therapies. The objective of this robust pragmatic literature review was to identify and describe recent studies on the HRQoL burden of NASH from the patient perspective. METHODS: English-language primary research studies were identified that measured HRQoL in adults with NASH (population-based studies or clinical trials of pharmacological therapy). Searches were conducted in the following bibliographical databases: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), and Health Technology Assessment Database (HTA). Abstracts from selected congresses (2015/2016) were hand searched. Articles were assessed for relevance by two independent reviewers, and HRQoL data were extracted. RESULTS: A total of 567 de-duplicated abstracts were identified, and 20 full-text articles were reviewed. Eight studies were included: five quantitative, two interventional, and one qualitative. The quantitative and interventional studies measured HRQoL using the Short-Form 36 (SF-36) and the Chronic Liver Disease Questionnaire (CLDQ), and the qualitative study involved focus groups and individual interviews. Overall, the studies showed that NASH affects HRQoL, especially physical functioning, with many patients reporting being fatigued. In quantitative studies, overall, patients with NASH had a reduced HRQoL versus normative populations and nonalcoholic fatty liver disease (NAFLD) patients, but not versus chronic liver diseases. A longitudinal study showed that when weight loss was achieved, HRQoL improvement over 6 months was greater in patients with NASH versus NAFLD. Qualitative research suggested that, in addition to fatigue, other symptoms are also burdensome, having a broad negative impact on patients' lives. The impact of pharmacological treatment on HRQoL was explored in only two included studies. CONCLUSIONS: HRQoL is impaired in patients with NASH. Patients experience a range of symptoms, especially fatigue, and the impact on their lives is broad. Further research is needed to understand the HRQoL burden of NASH (e.g. assessing NASH-specific impacts not captured by SF-36 and CLDQ) and the impact of future NASH therapies on HRQoL.

Impact of hypoglycaemia on quality of life and productivity in type 1 and type 2 diabetes.

AIM: To characterise the impact of increasing severity and frequency of hypoglycaemia on utility, quality of life, primary care resource use and productivity (time away from normal activities) in people with both Type 1 and Type 2 diabetes. METHODS: A postal survey was sent to 3200 people with diabetes. Self-reported episodes of mild, moderate, severe and nocturnal hypoglycaemia were quantified from a list of signs and symptoms. A number of instruments were used to explore the effect of frequency and severity of hypoglycaemia on quality of life and productivity. RESULTS: There were 861 respondents for whom diabetes type was identifiable. Of these respondents, 629 (73%) experienced some form of hypoglycaemia, 516 (60%) non-exclusively experienced mild or moderate hypoglycaemia, 57 (7%) experienced severe hypoglycaemia and 191 (22%) experienced nocturnal hypoglycaemia. Quality of life and health-related utility decreased as the frequency and severity of hypoglycaemia increased. The use of primary care resources and lost productivity increased as the severity and frequency of hypoglycaemia increased. These associations were independent in multivariate analysis. CONCLUSIONS: These findings suggest hypoglycaemia impacts heavily on the well-being, productivity and quality of life of people with diabetes, and that every effort should be made to minimise hypoglycaemia while aiming for good glycaemic control.

Utility values in diabetic kidney disease: a literature review.

OBJECTIVE: To summarize the published literature on utilities for health states associated with diabetic kidney disease (DKD), including end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS: A literature review was conducted (MEDLINE, MEDLINE in process, EMBASE, NHS EED, HEED, CEA Registry, EconLit, RePEc, and HTA) to identify relevant articles published between January 2000 and July 2013. Results were assessed for relevance by two reviewers in line with the study protocol. MAIN OUTCOME MEASURES: For eligible studies, data extracted included patient population, health states, methods used to elicit utility values, and the source of the preference values. RESULTS: Twelve studies satisfied the inclusion criteria. They reported various utility and/or disutility scores for different DKD health states using a range of patient populations, utility approaches, and sources of preference values. The most common study country was the USA. Most of the studies collected data at one time point, but two had a longitudinal design. Three different utility instruments - EuroQoL (EQ-5D), Quality of Well-Being Scale (QWB), and 15-dimensional (15D) - were used to elicit utilities indirectly. The Time Trade-Off (TTO) approach was used in one study; another undertook a meta-analysis of published utility studies. Utilities were identified for different health states including DKD, ESRD-no dialysis, ESRD-dialysis, and transplant. One study reported utilities for patients by type of transplant. There was variation in values for the same health state between studies, and none of the studies reported utilities for the different stages of DKD. In the studies that undertook a comparison, utility values for those with DKD were generally found to be lower than those without DKD. CONCLUSIONS: This literature review highlights that at present utility scores (or disutility penalties) exist for relatively few health states in DKD. Further studies are needed to produce accurate and comprehensive utility scores that differentiate between different DKD health states.

A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results.

Randomized controlled trials (RCTs) are conducted under idealized and rigorously controlled conditions that may compromise their external validity. A literature review was conducted of published English language articles that reported the findings of studies assessing external validity by a comparison of the patient sample included in RCTs reporting on pharmaceutical interventions with patients from everyday clinical practice. The review focused on publications in the fields of cardiology, mental health, and oncology. A range of databases were interrogated (MEDLINE; EMBASE; Science Citation Index; Cochrane Methodology Register). Double-abstract review and data extraction were performed as per protocol specifications. Out of 5,456 de-duplicated abstracts, 52 studies met the inclusion criteria (cardiology, n = 20; mental health, n = 17; oncology, n = 15). Studies either performed an analysis of the baseline characteristics (demographic, socioeconomic, and clinical parameters) of RCT-enrolled patients compared with a real-world population, or assessed the proportion of real-world patients who would have been eligible for RCT inclusion following the application of RCT inclusion/exclusion criteria. Many of the included studies concluded that RCT samples are highly selected and have a lower risk profile than real-world populations, with the frequent exclusion of elderly patients and patients with co-morbidities. Calculation of ineligibility rates in individual studies showed that a high proportion of the general disease population was often excluded from trials. The majority of studies (n = 37 [71.2 %]) explicitly concluded that RCT samples were not broadly representative of real-world patients and that this may limit the external validity of the RCT. Authors made a number of recommendations to improve external validity. Findings from this review indicate that there is a need to improve the external validity of RCTs such that physicians treating patients in real-world settings have the appropriate evidence on which to base their clinical decisions. This goal could be achieved by trial design modification to include a more representative patient sample and by supplementing RCT evidence with data generated from observational studies. In general, a thoughtful approach to clinical evidence generation is required in which the trade-offs between internal and external validity are considered in a holistic and balanced manner.

Vision-specific instruments for the assessment of health-related quality of life and visual functioning: a literature review.

Clinically objective measures such as visual acuity or visual field provide an assessment of a patient's visual status. However such measures may not reflect the degree of visual impairment the patient experiences in his or her daily activities. Visual impairment has been shown to have negative effects on health-related quality of life (HR-QOL) and a significant impact on daily functioning, including social activities. As such, there is a growing recognition of the importance of patient-reported outcomes of visual functioning. This review examines the development and psychometric properties of 22 vision-specific instruments assessing visual functioning and/or the impact of visual impairment on HR-QOL or daily activities. Issues relevant to assessing vision-specific subjective outcomes are reviewed, with specific application of the reviewed instruments. Three instruments, the Activities of Daily Vision Scale, National Eye Institute Visual Function Questionnaire, and Visual Function Index have been well validated and widely used, but others also show promise. To fully capture the benefits of a new ophthalmology treatment (or new treatment for eye disease) a valid and reliable visual instrument, in which the psychometric performance has been demonstrated in the particular ocular condition being treated, should be utilised.

The influence of diabetic retinopathy on quality of life: interviews to guide the design of a condition-specific, individualised questionnaire: the RetDQoL.

An individualised measure of the impact of diabetic retinopathy on quality of life (QoL) was developed, using a four-phase iterative approach, incorporating qualitative and quantitative methods. In semi-structured interviews, eleven people with diabetic retinopathy in each of two UK and two German hospitals described how QoL would be different without diabetic retinopathy. They completed and commented on the latest Retinopathy Dependent QoL (RetDQoL) draft. Interviews were content analysed before questionnaire revision and translation for the next centre. Twenty-six men and 18 women were interviewed: median age 60.5 (28-82) years; severity ranged from untreated background diabetic retinopathy to proliferative diabetic retinopathy requiring photocoagulation in both eyes, and vitrectomy. The resulting 26-domain RetDQoL asks about the impact of 'diabetic eye problems'. Iterative methodology ensured good understanding, face and content validity. It can be self- or interviewer-completed. Visual impairment, worries and movement restrictions impaired many aspects of QoL, with impacts before vision loss. Practice implications relate to using the RetDQoL and improving practitioner-patient communication.

The Health Technology Assessment Environment in Mainland China, Japan, South Korea, and Taiwan-Implications for the Evaluation of Diabetes Mellitus Therapies.

BACKGROUND: Diabetes mellitus (DM) is associated with a significant global economic and humanistic burden. The condition presents a real challenge in Asia, which accounts for more than 60% of individuals with DM globally. Health technology assessment (HTA) is a field of scientific research used to inform policy and clinical decision making relating to the introduction and diffusion of health technologies. OBJECTIVES: This article, examines the present use and predicted evolution of HTA with respect to pricing and reimbursement of drugs in mainland China, Japan, South Korea, and Taiwan. It makes specific reference to important assessment considerations for DM therapies, which should assist key stakeholders in choosing which data to capture, and what approaches to use, to help quantify the value of treatment. METHODS: The findings are informed by two Advisory Board discussions, a literature review, and the authors' personal experience. RESULTS: HTA already has a key role in South Korea and Taiwan, with current systems undergoing important changes. In contrast, in mainland China and Japan, HTA is not yet formally utilized, although this appears likely to change. Several elements are important for HTA to be meaningful and impactful for DM therapies, including a clear, transparent analytical framework for HTA that includes all relevant costs and outcomes; availability of local DM epidemiologic, economic, and quality-of-life data; acceptance of modeling as a core methodology; availability of real-life patient data; and recognition of specific evidence requirements associated with biosimilars. HTA has the potential to assist payors in making informed decisions about the coverage of DM medications.

Systematic review of efficacy of rFVIIa and aPCC treatment for hemophilia patients with inhibitors.

INTRODUCTION: The primary treatment for mild-to-moderate bleeding disorders in hemophilia is either recombinant activated factor VII (rFVIIa) or activated prothrombin complex concentrate (aPCC). The efficacy of both products has been evaluated in individual studies; however, there has not been an overall review to compare the efficacy from these individual studies of rFVIIa and aPCC. Our aim is to establish robust estimates of the efficacy, speed of bleed resolution, and adverse event profile of both rFVIIa and aPCC. METHODS: A systematic review was conducted of the relevant literature. RESULTS: We identified 11 open-label cohort studies, six randomized clinical trials, including two head-to-head clinical trials, and a meta-analysis. The definition of efficacy varies between these studies, but is usually a composite measure of definite pain relief, reduction in the size of the hemorrhage, and cessation of bleeding. The individual making the interpretation of efficacy and the time from treatment initiation to recording the efficacy endpoint also varies across the studies. Overall, estimates of efficacy from randomized clinical trials using dosing regimens in line with the guidelines are higher for rFVIIa (81%-91%) than for aPCC (64%-80%). Conclusions from a meta-analysis suggest that treatment with rFVIIa may be associated with a faster time to joint bleed resolution than aPCC due to higher efficacy levels at different time points. The results from a comparative trial support the improved efficacy rates associated with rFVIIa compared with aPCC. CONCLUSION: The wide variations in definitions of efficacy and study methods make comparison of results across studies difficult. Further head-to-head trials should incorporate a standardized measurement for defining efficacy.

The impact of diabetic retinopathy: perspectives from patient focus groups.

BACKGROUND: Diabetic retinopathy (DR) affects 50-85% of people with diabetes and may result in visual impairment or blindness. OBJECTIVE: This exploratory qualitative research was conducted to evaluate the symptom experience of DR, its impact on daily activities and health-related quality of life (HRQL), and the applicability of two vision-specific questionnaires. METHODS: Four focus groups (n = 15) were conducted with people with DR to explore their symptom experience and the impact on functioning and HRQL. Adults with type I or II diabetes and mild, moderate or severe non-proliferative DR (NPDR) or proliferative DR (PDR) were recruited. Content analysis and descriptive statistics were used to analyse the data. RESULTS: Participants described a range of symptoms and impact. Difficulty driving, especially at night, and trouble reading were noted with all levels of severity. Participants with PDR and decreased visual acuity have foregone many other important life aspects such as work, reading and sports. For the severely affected, diabetic care activities (e.g. exercising, reading nutritional labels, preparing insulin injections and glucose testing) were difficult to accomplish. Loss of independence, especially mobility and increased fear of accidents, had a profound impact on social activities. For those patients who had not experienced other complications of diabetes, the threat of vision loss was the most devastating. CONCLUSION: The loss of independence and mobility associated with decreased visual functioning and visual loss were major concerns. Moderate, severe NPDR and PDR associated with visual impairment have a significant impact on HRQL, particularly in the areas of independence, mobility, leisure and self-care activities.