Elena Nicod

Pars plana vitrectomy for vitreomacular traction syndrome: a systematic review and metaanalysis of safety and efficacy

Purpose: To determine the safety and efficacy of pars plana vitrectomy for vitreomacular traction. Methods: Articles reporting visual acuity change before and after pars plana vitrectomy were selected using a systematic literature review with predefined eligibility criteria. Visual acuities were converted to logarithm of the minimum angle of resolution (logMAR), weighted for study size, and pooled across studies. Safety outcomes were also pooled across studies. Results: Twenty-one of 460 articles were eligible. Mean (±standard deviation) logMAR visual acuity improved from 0.67 ± 0.55 to 0.42 ± 0.45 (n = 259 eyes) after pars plana vitrectomy (from 20/94 to 20/53 Snellen). In series of at least 20 eyes, mean visual acuity improved in all 5 studies (sign test, P = 0.0625). Of 392 eyes, 9.2% lost visual acuity, 11.7% were unchanged, and 64.3% improved; 32.9% of 217 eyes gained ≥2 Snellen lines. The most common postoperative complications were cataract (34.7% of 304 eyes; 63.2% of 68 phakic eyes), epiretinal membrane (5.7% of 348 eyes), and retinal detachment (4.6% of 348 eyes). Cataract surgery was undertaken in 10.5% of eyes. Conclusion: The visual acuity gains after pars plana vitrectomy for vitreomacular traction are relatively modest, but visual acuity change may not fully reflect symptomatic relief.

Symptomatic vitreomacular adhesion.

Background: Symptomatic vitreomacular adhesion describes symptomatic loss of visual function as a result of vitreous traction at the macula. Methods: Literature review. Results: Symptomatic vitreomacular adhesion can occur in isolation as vitreomacular traction, which may lead to the development of a macular hole, or it may occur alongside epiretinal membrane. It is likely to be associated with age-related macular degeneration and possibly diabetic maculopathy, although this is less certain. The treatment depends largely on the cause, but options include observation, vitrectomy, and pharmacologic vitreolysis. Small uncontrolled trials have also explored the use of an intravitreal gas bubble as a means of releasing VMA. If all cases of sVMA are considered together, then the burden of illness is substantial, with a prevalence of ∼0.35 per 100 population (excluding epiretinal membrane). Furthermore, there may be many more cases of undiagnosed sVMA. Conclusion: The recent introduction of ocriplasmin is likely to increase interest in sVMA. Clinical trials suggest that it has a role in the treatment of vitreomacular traction and Stages 1 to 3 macular holes but not primarily as a treatment of epiretinal membrane. Its role in other diseases associated with VMA remains to be determined.

Commonalities and differences in HTA outcomes: A comparative analysis of five countries and implications for coverage decisions

OBJECTIVE To identify diverging HTA recommendations across five countries, understand the rationale for decision-making in specific therapeutic categories, and suggest ways forward to minimize these inter-country differences. METHODS A comparative analysis of HTA recommendations for 287 drug-indication pairs appraised by five countries (England, Scotland, Sweden, Canada, and Australia) between 2007 and 2009, including an in-depth analysis of two case studies. Agreement levels were measured using kappa scores. Associations were explored through correspondence analysis. RESULTS Significant inter-country variability in the HTA recommendations exists: 46% of the drug-indication pairs studied received diverging recommendations across countries. The level of agreement between agencies was poor to moderate. Associations between HTA recommendations issued by each HTA body per therapy area (cancer, orphan, CNS) differed from the general pattern observed across the complete sample. Expectations from HTA bodies in terms of relative effectiveness differ depending on the drug and diseases characteristics, although agency-specific guidelines are homogeneous for all treatments. POLICY IMPLICATIONS Distinguishing and accounting for the specifics underpinning individual conditions and their characteristics in HTA processes may constitute a way forward to improved HTA methods, while increasing transparency in the expectations that HTA bodies have in terms of relative effectiveness of the drug depending on these characteristics.

Vitreous attachment in age-related macular degeneration, diabetic macular edema, and retinal vein occlusion: a systematic review and metaanalysis.

Purpose: To determine if there is an association of vitreous attachment and wet age-related macular degeneration (AMD), diabetic macular edema, and retinal vein occlusion. Methods: Systematic review and metaanalysis. Results: Sixteen of 1,025 articles were eligible. In wet AMD, the prevalence of vitreomacular adhesion and posterior vitreous detachment was 23% (654 eyes) and 41% (251), respectively. Vitreomacular adhesion prevalence was 2.15 times that of controls (95% confidence interval, 1.34–3.48; p = 0.002) and 2.54 times that of dry AMD (confidence interval, 0.88–7.36; p 0.09); posterior vitreous detachment prevalence was lower than controls (relative risk 0.77; confidence interval, 0.64–0.93; p = 0.007) and dry AMD (0.56; confidence interval, 0.27–1.14; p = 0.11). It was not possible to determine the prevalence of vitreous attachment in diabetic macular edema, but vitreomacular traction was present in 29% of 188 surgical cases. The prevalence of posterior vitreous detachment in eyes with central and branch retinal vein occlusion was 30% (56 eyes) and 31% (71 eyes), respectively, versus 25% (64 eyes) in controls. Conclusion: Observational studies of sufficient quality indicate that eyes with wet AMD have double the expected prevalence of vitreomacular adhesion and are less likely to have a posterior vitreous detachment. More controlled studies of diabetic macular edema and retinal vein occlusion are needed.

Social and economic costs and health-related quality of life in non-institutionalised patients with cystic fibrosis in the United Kingdom.

BackgroundThis study aimed to determine the societal economic burden and health-related quality of life (HRQOL) of cystic fibrosis (CF) patients in the UK.MethodsA bottom-up cost-of-illness, cross-sectional, retrospective analysis of 74 patients was conducted aiming to estimate the economic impact of CF. Data on demographic characteristics, health resource utilisation, informal care, productivity losses and HRQOL were collected from questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D) instrument.ResultsUsing unit costs for 2012 we found that the average annual cost for a CF patient was €48,603, with direct health care costs amounting to €20,854 (42.9 % of total costs), direct non-health care costs being €21,528 (44.3 %) and indirect costs attributable to productivity losses being €6,222 (12.8 %). On average, the largest expenditures by far were accounted for by informal care (44.1 %), followed by medications (14.5 %), acute hospitalisations (13.9 %), early retirement (9.1 %) and outpatient and primary health care visits (7.9 %). Sharp differences existed depending on whether CF patients were in need of caregiver help (€76,271 versus €26,335). In adult CF patients, mean EQ-5D index scores were 0.64 (0.93 in the general population) and mean EQ-5D visual analogue scale scores were 62.23 (86.84 in the general population); among caregivers, these scores were 0.836 and 80.85, respectively.DiscussionOur analysis highlights the importance of the economic and quality of life consequences of CF from a societal perspective. The results highlight that beyond conventional costs such as acute hospitalisations, medication and outpatient and primary care visits, indirect costs related to informal care and early retirement, have significant societal implications. Similarly, our analysis showed that the average EQ-5D index score of adult CF patients was significantly lower than in the general population, an indication that a methodological bias may exist in using the latter in economic analyses.ConclusionCF poses a significant cost burden on UK society, with non-health care and indirect costs representing 57 % of total average costs, and HRQOL being considerably lower than in the general population.

Pars plana vitrectomy for diabetic macular edema: a systematic review, meta-analysis, and synthesis of safety literature

Purpose: To assess the risk and benefit of pars plana vitrectomy for diabetic macular edema. Methods: The authors conducted a systematic literature review using PubMed, EMBASE, Web of Science, and Cochrane Central Database of Controlled Trials until September 2014. The population was patients with diabetic macular edema, intervention vitrectomy, comparator macular laser or observation, and efficacy outcome visual acuity and central retinal thickness. Safety outcomes were intraoperative and postoperative surgical complications. The efficacy meta-analysis included only randomized controlled trials. The safety analysis included prospective, retrospective, controlled, and uncontrolled studies. Results: Five studies were eligible for the efficacy meta-analysis (n = 127 eyes) and 40 for the safety analysis (n = 1,562 eyes). Combining follow-up intervals from 6 to 12 months, the meta-analysis found a nonsignificant 2 letter visual acuity difference favoring vitrectomy, and a significant 102 &mgr;m greater reduction in central retinal thickness favoring vitrectomy, but a post hoc subgroup analysis found that a 6-month central retinal thickness benefit reversed by 12 months. The most frequent complications were retinal break (7.1%), elevated intraocular pressure (5.2%), epiretinal membrane (3.3%), and vitreous hemorrhage (2.4%). Cataract developed in 68.6% of 121 phakic eyes. Conclusion: Vitrectomy produces structural and functional improvements in select eyes with diabetic macular edema, but the visual gains are not significantly better than with laser or observation. No major safety concerns were identified.

HTA programme response to the challenges of dealing with orphan medicinal products: Process evaluation in selected European countries

BACKGROUND Challenges commonly encountered in HTA of orphan medicinal products (OMPs) were identified in Advance-HTA. Since then, new initiatives have been developed to specifically address issues related to HTA of OMPs. OBJECTIVE AND METHODS This study aimed to understand why these new HTA initiatives in England, Scotland and at European-level were established and whether they resolve the challenges of OMPs. The work of Advance-HTA was updated with a literature review and a conceptual framework of clinical, regulatory and economic challenges for OMPs was developed. The new HTA programmes were critiqued against the conceptual framework and outstanding challenges identified. RESULTS The new programmes in England and Scotland recognise the challenges identified in demonstrating the value of ultra-OMPs (and OMPs) and that they require a different process to standard HTA approaches. Wider considerations of disease and treatment experiences from a multi-stakeholder standpoint are needed, combined with other measures to deal with uncertainty (e.g. managed entry agreements). While approaches to assessing this new view of value of OMPs, extending beyond cost/QALY frameworks, differ, their criteria are similar. These are complemented by a European initiative that fosters multi-stakeholder dialogue and consensus about value determinants throughout the life-cycle of an OMP. CONCLUSION New HTA programmes specific to OMPs have been developed but questions remain about whether they sufficiently capture value and manage uncertainty in clinical practice.

Dealing with Uncertainty and Accounting for Social Value Judgments in Assessments of Orphan Drugs: Evidence from Four European Countries

OBJECTIVES To better understand the reasons for differences in reimbursement decisions for orphan drugs in four European countries that were not readily apparent from health technology assessment (HTA) reports and operating procedures. METHODS Semistructured interviews with representatives of HTA bodies in England, Scotland, Sweden, and France were conducted. An interview topic guide was developed on the basis of findings from a systematic comparison of HTA decisions for 10 orphan drugs. Qualitative thematic data analysis was applied to the interview transcripts using the framework approach. RESULTS Eight representatives from the four HTA bodies were interviewed between March and June 2015. Evidentiary requirements and approaches to dealing with imperfect or incomplete evidence were explored, including trial design and duration, study population and subgroups, comparators, and end points. Interviewees agreed that decisions regarding orphan drugs are made in a context of lower quality evidence, and the threshold of acceptable uncertainty varied by country. Some countries imposed higher evidentiary standards for greater clinical claims, which may be more challenging for orphan diseases. The acceptability of surrogate end points was not consistent across countries nor were the validation requirements. The most common social value judgments identified related to innovation, disease severity, and unmet need. Differences were seen in the way these concepts were defined and accounted for across countries. CONCLUSIONS Although agreement was seen in evidentiary requirements or preferences, there were subtle differences in the circumstances in which uncertain evidence may be considered acceptable, possibly explaining differences in HTA recommendations across countries.

Why Are There Differences In Hta Recommendations Across Countries? A Systematic Comparison of Hta Decision Processes for A Sample of Orphan Drugs In Four Countries.

Orphan Drugs, only the Eculizumabe for the treatment of PNH has no approved registration by the National Health Surveillance Agency (ANVISA). ConClusions: Considering its high cost, high judicial demand and limited availability of scientific evidence, orphan drugs represent a challenge for researchers and decision makers. Clinical benefit, disease severity, availability of therapeutic alternatives, ethical, political and social aspects should be considered. It is necessary to start a multidisciplinary reflection on the development of HTA models and policies regarding rare diseases and innovative treatments in the SUS, as well as fostering the primary researches in this field.