DEFINING ELIGIBILITY CRITERIA FOR FUNDING POLICIES AROUND IN VITRO FERTILIZATION.

OBJECTIVES: This review aims to assess the state of the science around the potential impact of certain patient characteristics on the safety and effectiveness of in vitro fertilization (IVF). METHODS: Following Cochrane Collaboration guidelines and the PRISMA statement, a comprehensive systematic review of reviews and recent primary studies examining the impact of paternal age and maternal age, smoking, and body mass index (BMI) on the safety and effectiveness of IVF was performed. Papers, published between January 2007 and June 2014, were independently reviewed and critically appraised by two researchers using published quality assessment tools for reviews and primary studies. Due to heterogeneity across papers (different study designs and patient selection criteria), a qualitative analysis of extracted information was performed. RESULTS: Seventeen papers (ten systematic reviews and seven primary studies) were included. They comprised evidence from retrospective observational studies in which maternal age, BMI, and smoking status were explored as part of secondary analyses of larger studies. The majority of papers found that the likelihood of achieving a pregnancy was lower among women who were >40 years, had a BMI ≥ 25 and smoked. Advanced maternal age and BMI were also associated with higher rates of preterm birth and low birth weight. CONCLUSIONS: Based on available evidence, it may be appropriate to consider "maternal age" and "morbid obesity" in public funding policies that aim to maximize the effectiveness of IVF. However, given inconsistencies in the effect of smoking across different pregnancy-related outcomes, support for incorporating it into funding conditions appears weak.

Assisted Reproductive Technologies in Alberta: An Economic Analysis to Inform Policy Decision-Making.

OBJECTIVE: Regulation and public funding of assisted reproductive technologies (ARTs) vary across the Canadian provinces. In Alberta, neither of these exists. We conducted this study to evaluate the cost effectiveness and budget impact of providing ARTs in Alberta under three different policy scenarios (a "restrictive" policy, a policy based on Quebec's model, and a "permissive" policy) in comparison with the status quo. METHODS: To predict the cost effectiveness and budget impact of three policy options for publicly funded ARTs in Alberta, we developed an economic model by combining a state transition Markov model and a decision tree. The primary outcome was cost per healthy singleton. Probabilistic and one-way sensitivity analyses were conducted. RESULTS: The restrictive policy was the most cost effective option for two subgroups of age (< 35 years and 35 to 39 years), while the Quebec policy option was most cost-effective for the ≥ 40 years subgroup. Budget impact analysis extending up to the age of 18 years for the children in the model showed the cost savings of $8.33 million for the restrictive policy for the < 35 years subgroup. For the ≥ 40 years subgroup, the Quebec policy option resulted in total cost savings of $3.75 million. Sensitivity analyses showed that the model results were robust. CONCLUSION: This economic modelling study shows that publicly funded and scientifically regulated ARTs could provide treatment access and save health care expenditures for the province.

Objectif : La réglementation et le financement public des techniques de procréation assistée (TPA) varient d'une province canadienne à l'autre. En Alberta, les TPA ne sont ni réglementées ni financées par les deniers publics. Nous avons mené cette étude dans le but d'évaluer la rentabilité de l'offre de TPA en Alberta et les effets d'une telle mesure sur le budget albertain en fonction de trois scénarios de politique différents (une politique « restrictive ¼, une politique fondée sur le modèle québécois et une politique « permissive ¼), par comparaison avec le statu quo. Méthodes : Pour prédire la rentabilité de ces trois options de politique (prévoyant l'offre de TPA financées par les deniers publics en Alberta) et leurs effets sur le budget provincial, nous avons élaboré un modèle économique en combinant un modèle Markov (transitions d'état) et un arbre décisionnel. Le coût par nouveau-né en santé issu d'une grossesse monofœtale constituait le critère d'évaluation principal. Des analyses simples de la variance en matière de sensibilité et des analyses probabilistes ont été menées. Résultats : La politique « restrictive ¼ a constitué l'option la plus rentable dans deux sous-groupes d'âge (< 35 ans et 35-39 ans), tandis que la politique fondée sur l'approche québécoise a constitué l'option la plus rentable dans le sous-groupe des ≥ 40 ans. L'analyse des effets sur le budget (jusqu'à ce que les enfants générés par le modèle ait atteint l'âge de 18 ans) a indiqué l'obtention d'économies de 8,33 millions de dollars pour ce qui est de la politique « restrictive ¼ dans le sous-groupe des < 35 ans. Dans le sous-groupe des ≥ 40 ans, l'option de la politique fondée sur l'approche québécoise a mené à l'obtention d'économies totales de 3,75 millions de dollars. Les analyses de la sensibilité ont indiqué que les résultats modélisés étaient robustes. Conclusion : Cette étude de modélisation économique indique que l'offre de TPA financées par les deniers publics et faisant l'objet d'une réglementation scientifique pourrait assurer l'accès au traitement et permettre l'obtention d'économies pour la province.

Introduction of a new health technology into a provincial health system: A case study of insulin pump therapy.

Decisions on the introduction of new non-drug health technologies into healthcare are challenging. This article describes the introduction of insulin pump therapy for type 1 diabetes in Alberta, using an Access with Evidence Development (AED) approach. The organization and implementation of the AED, its current status, and lessons learned are described.

Assisted reproductive technologies (ARTs): evaluation of evidence to support public policy development.

Over the years, IVF/ICSI protocols have continued to evolve with efforts to improve outcomes. As a result, treatment success may be related to certain procedural factors, including number of embryos transferred and stage at which they are transferred. This review aims to assess the safety and effectiveness of IVF/ICSI in comparison to spontaneous conception and less invasive ARTs and the impact of procedure-related factors on the outcomes of IVF/ICSI in order to support the development of local clinical and policy guidance. Following Cochrane Collaboration guidelines and the PRISMA statement, a comprehensive systematic review of literature examining the impact of procedural characteristics on the safety or effectiveness of IVF/ICSI from 2007 to date was performed. 33 systematic reviews and 3 primary studies evaluating the impact of procedural differences, IVF/ICSI in comparison to less invasive ARTs, and ARTs in comparison to spontaneous conception were found. IVF was shown to offer significant benefits over no treatment and IUI in achieving pregnancy and live birth among couples with endometriosis or unexplained infertility. Frozen and blastocyst-stage embryo transfers were as effective as fresh and cleavage-stage embryo transfers, respectively. In comparison to single embryo transfer, double embryo transfer significantly increased pregnancy, live birth and multiple pregnancy/birth rates. IVF/ICSI was associated with more complications during pregnancy and delivery, and in infants compared to naturally conceived pregnancies, particularly when multiple embryo transfer was used. Frozen embryo transfer had fewer adverse events during pregnancy and delivery than fresh embryo transfer, and was at least as safe in terms of infant outcomes. The potential complications of IVF/ICSI may be minimized through procedural choices, but such choices often impact effectiveness. Thus, in developing clinical and policy guidance around IVF/ICSI, the risk-benefit trade-offs patients and providers are willing to accept must be carefully considered.

A systematic review of the safety and effectiveness of fully implantable middle ear hearing devices: the carina and esteem systems.

OBJECTIVE: To examine the safety and effectiveness of fully implantable middle ear devices in the treatment of hearing loss. DATA SOURCES: MEDLINE, EMBASE, The Cochrane Library, Web of Science, CINAHL, PsycINFO, and the Centre for Reviews and Dissemination were searched without date or language limits. STUDY SELECTION: Titles and abstracts of 7,700 citations were screened, and 30 articles were selected for full review, of which, 7 articles on the Esteem and 13 on the Carina met the study's eligibility criteria. DATA EXTRACTION: Information was extracted using a pretested data abstraction form, and study quality was assessed using the Oxford Centre for Evidence-Based Medicine Levels of Evidence. DATA SYNTHESIS: Because of heterogeneity across studies, meta-analysis was not performed, and comparisons were made by structured review. CONCLUSION: The majority of studies were quasi-experimental, prepost comparisons of aided and unaided conditions. Complication rates with the Esteem were higher than with the Carina, and most commonly included taste disturbance. However, device failure was common with the Carina, predominately related to charging difficulties. For both devices, clinically significant improvements in functional gain, speech reception, and speech recognition over the unaided condition were found. In studies comparing the Esteem or Carina to hearing aids, findings were mixed. Although improvements in functional gain were similar to those for hearing aids, speech recognition and quality of life were greater with the implants. Despite limited evidence, these devices seem to offer a relatively safe and effective treatment option, particularly for patients who are medically unable to wear conventional hearing aids.

Access with evidence development: an approach to introducing promising new technologies into healthcare.

The rapid development of new health technologies for which there is limited, but promising, evidence has resulted in a daunting challenge - to provide care that meets population health needs and optimizes patient outcomes, demonstrates an efficient use of healthcare resources, and upholds basic principles of equity, access, and choice. In this paper, we introduce 'Access with Evidence Development' as a possible mechanism for addressing this challenge and discuss its application to the "Zamboni procedure" for Multiple Sclerosis.

Effectiveness of photodynamic therapy for mammary and extra-mammary Paget's disease: a state of the science review.

BACKGROUND: Paget's disease is a rare skin disorder occurring in the breast (mammary) or in the groin, genital, peri-anal and axillary regions (extra-mammary). Typical treatment involves surgical excision, which in the case of extra-mammary Paget's disease, can lead to significant morbidity. Photodynamic therapy (PDT) which uses a topical or intravenous photosensitizing agent that is activated by a light source to ablate abnormal tissue, offers a minimally invasive alternative. The purpose of this study was to assess the effectiveness of photodynamic therapy in the treatment of Paget's disease. METHODS: Following Cochrane guidelines, a comprehensive systematic review of all clinical studies and reports examining the use of PDT for mammary and extra-mammary Paget's disease was conducted. Study quality was assessed using the Oxford Levels of Evidence Scale. RESULTS: 21 retrospective and 2 prospective non-comparative studies were identified and included in the review: 9 case reports with 1-2 patients and 14 case series with 1-16 patients. These reports totalled 99 patients with 133 extra-mammary Paget's lesions and 3 patients (with 3 lesions) with mammary Paget's disease. Follow-up periods were typically one year or less, with 77/133 extra-mammary lesions exhibiting complete response to PDT. One recurrent mammary skin lesion and two mammary lesions treated concomitantly with surgery also exhibited complete responses. CONCLUSIONS: Evidence of the effectiveness of PDT for Paget's disease is promising, but limited. This may, in part, be explained by the rarity of the condition, making controlled comparative clinical trials challenging.

Extensive deep gray matter volume reductions in children and adolescents with fetal alcohol spectrum disorders.

BACKGROUND: The link between the numerous cognitive, motor, and behavioral difficulties of individuals with fetal alcohol spectrum disorders (FASD) and underlying specific structural brain injuries can be investigated using high-resolution imaging. Differential sensitivity of the brain's "relay" stations, namely the deep gray matter structures, may play a key factor given their multifaceted role in brain function. The purpose of our study was to analyze differences in deep gray matter volumes of children and adolescents with FASD relative to age/sex-matched controls and to examine whether any volume differences were consistent across the age range of neurodevelopment. METHODS: Children and adolescents (N = 28, 6 to 17 years) diagnosed with FASD and 56 age- and sex-matched healthy controls (i.e., 2 matched controls per FASD subject) underwent 3-dimensional T1-weighted MRI scans that were used for the automated volume measurement (FreeSurfer) of the intracranial space, total white matter, cortical gray matter, and 6 deep gray matter structures, namely the hippocampus, amygdala, thalamus, caudate, putamen, and globus pallidus, with left and right measured separately. Volumes were compared between FASD and controls, as well as changes with age. RESULTS: Significant reductions of volume in FASD were observed for the intracranial vault (7.6%), total white matter (8.6%), total cortical gray matter (7.8%), and total deep gray matter (13.1%). All 6 deep gray matter structures showed significant volume reductions bilaterally with the caudate (approximately 16%) and globus pallidus (approximately 18%) being most affected. The hippocampus, thalamus, and globus pallidus showed reductions in all 3 age subgroups (6 to 9, 10 to 13, and 14 to 17 years) but the caudate and putamen had smaller volumes for FASD only within the 2 youngest subgroups; the amygdala was only smaller for FASD in the 2 oldest subgroups. CONCLUSIONS: Significant, but variable, volume reductions throughout the deep gray matter are observed over a wide age range of 6 to 17 years in FASD.