Mireille Goetghebeur

Growth Hormone Research Society Workshop Summary: Consensus Guidelines for Recombinant Human Growth Hormone Therapy in Prader-Willi Syndrome

Context: Recombinant human GH (rhGH) therapy in Prader-Willi syndrome (PWS) has been used by the medical community and advocated by parental support groups since its approval in the United States in 2000 and in Europe in 2001. Its use in PWS represents a unique therapeutic challenge that includes treating individuals with cognitive disability, varied therapeutic goals that are not focused exclusively on increased height, and concerns about potential life-threatening adverse events. Objective: The aim of the study was to formulate recommendations for the use of rhGH in children and adult patients with PWS. Evidence: We performed a systematic review of the clinical evidence in the pediatric population, including randomized controlled trials, comparative observational studies, and long-term studies (>3.5 y). Adult studies included randomized controlled trials of rhGH treatment for ≥ 6 months and uncontrolled trials. Safety data were obtained from case reports, clinical trials, and pharmaceutical registries. Methodology: Forty-three international experts and stakeholders followed clinical practice guideline development recommendations outlined by the AGREE Collaboration (www.agreetrust.org). Evidence was synthesized and graded using a comprehensive multicriteria methodology (EVIDEM) (http://bit.ly.PWGHIN). Conclusions: Following a multidisciplinary evaluation, preferably by experts, rhGH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental, and lifestyle interventions. Cognitive impairment should not be a barrier to treatment, and informed consent/assent should include benefit/risk information. Exclusion criteria should include severe obesity, uncontrolled diabetes mellitus, untreated severe obstructive sleep apnea, active cancer, or psychosis. Clinical outcome priorities should vary depending upon age and the presence of physical, mental, and social disability, and treatment should be continued for as long as demonstrated benefits outweigh the risks.

Evidence and Value: Impact on DEcisionMaking – the EVIDEM framework and potential applications

BackgroundHealthcare decisionmaking is a complex process relying on disparate types of evidence and value judgments. Our objectives for this study were to develop a practical framework to facilitate decisionmaking in terms of supporting the deliberative process, providing access to evidence, and enhancing the communication of decisions.MethodsExtensive analyses of the literature and of documented decisionmaking processes around the globe were performed to explore what steps are currently used to make decisions with respect to context (from evidence generation to communication of decision) and thought process (conceptual components of decisions). Needs and methodologies available to support decisionmaking were identified to lay the groundwork for the EVIDEM framework.ResultsA framework was developed consisting of seven modules that can evolve over the life cycle of a healthcare intervention. Components of decision that could be quantified, i.e., intrinsic value of a healthcare intervention and quality of evidence available, were organized into matrices. A multicriteria decision analysis (MCDA) Value Matrix (VM) was developed to include the 15 quantifiable components that are currently considered in decisionmaking. A methodology to synthesize the evidence needed for each component of the VM was developed including electronic access to full text source documents. A Quality Matrix was designed to quantify three criteria of quality for the 12 types of evidence usually required by decisionmakers. An integrated system was developed to optimize data analysis, synthesis and validation by experts, compatible with a collaborative structure.ConclusionThe EVIDEM framework promotes transparent and efficient healthcare decisionmaking through systematic assessment and dissemination of the evidence and values on which decisions are based. It provides a collaborative framework that could connect all stakeholders and serve the healthcare community at local, national and international levels by allowing sharing of data, resources and values. Validation and further development is needed to explore the full potential of this approach.

From efficacy to equity: Literature review of decision criteria for resource allocation and healthcare decisionmaking.

ObjectivesResource allocation is a challenging issue faced by health policy decisionmakers requiring careful consideration of many factors. Objectives of this study were to identify decision criteria and their frequency reported in the literature on healthcare decisionmaking.MethodAn extensive literature search was performed in Medline and EMBASE to identify articles reporting healthcare decision criteria. Studies conducted with decisionmakers (e.g., focus groups, surveys, interviews), conceptual and review articles and articles describing multicriteria tools were included. Criteria were extracted, organized using a classification system derived from the EVIDEM framework and applying multicriteria decision analysis (MCDA) principles, and the frequency of their occurrence was measured.ResultsOut of 3146 records identified, 2790 were excluded. Out of 356 articles assessed for eligibility, 40 studies included. Criteria were identified from studies performed in several regions of the world involving decisionmakers at micro, meso and macro levels of decision and from studies reporting on multicriteria tools. Large variations in terminology used to define criteria were observed and 360 different terms were identified. These were assigned to 58 criteria which were classified in 9 different categories including: health outcomes; types of benefit; disease impact; therapeutic context; economic impact; quality of evidence; implementation complexity; priority, fairness and ethics; and overall context. The most frequently mentioned criteria were: equity/fairness (32 times), efficacy/effectiveness (29), stakeholder interests and pressures (28), cost-effectiveness (23), strength of evidence (20), safety (19), mission and mandate of health system (19), organizational requirements and capacity (17), patient-reported outcomes (17) and need (16).ConclusionThis study highlights the importance of considering both normative and feasibility criteria for fair allocation of resources and optimized decisionmaking for coverage and use of healthcare interventions. This analysis provides a foundation to develop a questionnaire for an international survey of decisionmakers on criteria and their relative importance. The ultimate objective is to develop sound multicriteria approaches to enlighten healthcare decisionmaking and priority-setting.

Bridging health technology assessment (HTA) and efficient health care decision making with multicriteria decision analysis (MCDA): applying the EVIDEM framework to medicines appraisal.

Background. Health care decision making is complex and requires efficient and explicit processes to ensure transparency and consistency of factors considered. Objectives. To pilot an adaptable decision-making framework incorporating multicriteria decision analysis (MCDA) in health technology assessment (HTA) with a pan-Canadian group of policy and clinical decision makers and researchers appraising 10 medicines covering 6 therapeutic areas. Methods. An appraisal group was convened and participants were asked to express their individual perspectives, independently of the medicines, by assigning weights to each criterion of the MCDA core model: disease severity, size of population, current practice and unmet needs, intervention outcomes (efficacy, safety, patient reported), type of health benefit, economics, and quality of evidence. Participants then assigned performance scores for each medicine using available evidence synthesized in a “by-criterion” HTA report covering each of the MCDA CORE model criteria. MCDA estimates of perceived value were calculated by combining normalized weights and scores. Feedback on the approach was collected through structured discussion. Results. Relative weights on criteria varied widely, reflecting the diverse perspectives of participants. Scores for each criterion provided a performance measure, highlighting strengths and weaknesses of each medicine. MCDA estimates of perceived value ranged from 0.42 to 0.64 across medicines, providing comprehensive measures incorporating a large spectrum of criteria. Participants reported that the framework provided an efficient approach to systematic consideration in a pragmatic format of the multiple elements guiding decision, including criteria and values (MCDA core model) and evidence (HTA “by-criterion” report). Conclusions. This proof-of-concept study demonstrated the usefulness of incorporating MCDA in HTA to support transparent and systematic appraisal of health care interventions. Further research is needed to advance MCDA-based approaches to more effective healthcare decision making.

Burden of rotavirus gastroenteritis in the Middle Eastern and North African pediatric population

BackgroundRotavirus gastroenteritis (RVGE) is the most common cause of severe childhood diarrhea worldwide. Objectives were to estimate the burden of RVGE among children less than five years old in the Middle East (Bahrain, Iran, Iraq, Israel, Jordan, Kuwait, Oman, Qatar, Saudi Arabia, Syria, UAE, Yemen), North Africa (Algeria, Egypt, Libya, Morocco, Tunisia) and Turkey.MethodsA comprehensive literature search was conducted in major databases on the epidemiology and burden of rotavirus among children less than five years old between 1999 and 2009. Data from each country was extracted and compared.ResultsThe search identified 43 studies. RVGE was identified in 16-61% of all cases of acute gastroenteritis, with a peak in the winter. RVGE-related hospitalization rates ranged from 14% to 45%, compared to 14%-28% for non-RVGE. Annually, RVGE caused up to 112 fatalities per 100,000 in certain countries in the region. Hospitalization costs ranged from

Burden of community-acquired and nosocomial rotavirus gastroenteritis in the pediatric population of Western Europe: a scoping review

1.8 to

Burden of rotavirus gastroenteritis in the pediatric population in central and eastern Europe Serotype distribution and burden of illness

4.6 million annually, depending on the country. The most recent literature available showed that G1P[8] was the most prevalent genotype combination in 8 countries (range 23%-56%). G2P[4] was most prevalent in 4 countries (26%-48%). G9P[8] and G4P[8] were also frequently detected.ConclusionsRVGE is a common disease associated with significant morbidity, mortality, and economic burden. Given the variety and diverse rotavirus types in the region, use of a vaccine with broad and consistent serotype coverage would be important to help decrease the burden of RVGE in the Middle East and North Africa.

Does technique matter; a pilot study exploring weighting techniques for a multi-criteria decision support framework

BackgroundRotavirus affects 95% of children worldwide by age 5 years and is the leading cause of severe dehydrating diarrhea. The objective of this review was to estimate the burden of rotavirus gastroenteritis (RVGE) in the Western European pediatric population.MethodsA comprehensive literature search (1999-2010) was conducted in PubMed and other sources (CDC; WHO, others). Data on the epidemiology and burden of RVGE among children < 5 years-old in Western Europe --including hospital-acquired disease--were extracted.Results76 studies from 16 countries were identified. The mean percentage of acute gastroenteritis (AGE) cases caused by rotavirus ranged from 25.3%-63.5% in children < 5 years of age, peaking during winter. Incidence rates of RVGE ranged from 1.33-4.96 cases/100 person- years. Hospitalization rates for RVGE ranged from 7% to 81% among infected children, depending on the country. Nosocomial RVGE accounted for 47%-69% of all hospital-acquired AGE and prolonged hospital stays by 4-12 days. Each year, RVGE incurred

Clinical and Economic Consequences of Vancomycin and Fidaxomicin for the Treatment of Clostridium difficile Infection in Canada

0.54-

Can the EVIDEM Framework Tackle Issues Raised by Evaluating Treatments for Rare Diseases: Analysis of Issues and Policies, and Context-Specific Adaptation

53.6 million in direct medical costs and