Cost-Consequence Analysis of Nitisinone for Treatment of Tyrosinemia Type I.

BACKGROUND: Tyrosinemia type I is a rare but severe genetic metabolic disorder. Nitisinone combined with a diet low in tyrosine and phenylalanine became first-line therapy in 1994. OBJECTIVES: To estimate the direct medical costs of health care services related to the treatment of tyrosinemia type I, taking into consideration the real-life efficacy of nitisinone. METHODS: A cost-consequence analysis was performed for all children with a confirmed diagnosis of tyrosinemia type I who were treated in Quebec between January 1, 1984, and January 1, 2009. The costs of care were compared for 3 consecutive historical groups: no nitisinone (1984 to 1994), late intervention with nitisinone (first dose received between 1994 and 1997), and early intervention with nitisinone (first dose received between 1997 and 2008). Data were derived from patient charts, hospital databases, and the Régie de l'assurance maladie du Québec and MED-ÉCHO administrative databases. Costs were reported in 2008 Canadian dollars. RESULTS: Nitisinone treatment was associated with significant reductions in the number and duration of hospital admissions, the number of admissions to a pediatric intensive care unit, and the number of liver transplants. The cost of hospitalization per person-year was significantly lower in the 2 groups treated with nitisinone: $673 and $5 590 for the early-intervention and late-intervention groups, respectively, as compared to $12 980 for the no-nitisinone group (p < 0.001). Hospital costs per person-year for liver transplant were $3 198 for the late-intervention group and $5 044 for the no-nitisinone group: there were no transplants in the early-intervention group. The cost of nitisinone per person-year was $51 493 for the early-intervention group and $64 895 for the late-intervention group. CONCLUSIONS: Nitisinone treatment significantly improved the outcomes of patients with tyrosinemia type I, while decreasing utilization of health care resources, liver transplants, and associated costs.

CONTEXTE: La tyrosinémie de type I est un trouble génétique du métabolisme rare, mais grave. La prise de nitisinone en association à un régime pauvre en tyrosine et en phénylalanine est devenue le traitement de première intention en 1994. OBJECTIFS: Offrir une estimation des coûts médicaux directs des services de santé liés au traitement de la tyrosinémie de type I, tout en tenant compte de l'efficacité réelle de la nitisinone. MÉTHODES: Une analyse coûts-conséquences a été réalisée pour chaque enfant ayant reçu un diagnostic de tyrosinémie de type I et ayant été traité au Québec entre le 1er janvier 1984 et le 1er janvier 2009. Les coûts des soins ont été comparés entre trois groupes historiques se suivant dans le temps : sans nitisinone (de 1984 à 1994), traitement tardif à la nitisinone (première dose reçue entre 1994 et 1997) et traitement précoce à la nitisinone (première dose reçue entre 1997 et 2008). Les données ont été obtenues à partir de dossiers médicaux de patients, de bases de données d'hôpitaux, de la base de données administrative de la Régie de l'assurance maladie du Québec et de la banque de données ministérielles MED-ÉCHO. Les coûts sont indiqués en dollars canadiens de 2008. RÉSULTATS: L'on a associé le traitement par nitisinone à d'importantes réductions : du nombre d'hospitalisations et de la durée des séjours à l'hôpital, du nombre d'admissions à l'unité de soins intensifs pédiatrique et du nombre de greffes hépatiques. Les coûts d'hospitalisation (par personne-année) étaient beaucoup plus faibles dans les deux groupes traités par nitisinone : 673 $ et 5 590 $ respectivement pour le groupe de traitement précoce et le groupe de traitement tardif, contre 12 980 $ pour le groupe sans traitement par nitisinone (p < 0,001). Les coûts d'hospitalisation (par personne-année) pour les greffes hépatiques étaient de 3 198 $ pour le groupe de traitement tardif et de 5 044 $ pour le groupe sans traitement par nitisinone; le groupe de traitement précoce n'a fait l'objet d'aucune greffe hépatique. Les coûts du traitement par nitisinone (par personne-année) étaient de 51 493 $ pour le groupe de traitement précoce et de 64 895 $ pour le groupe de traitement tardif. CONCLUSIONS: Le traitement par nitisinone améliore grandement les résultats thérapeutiques des patients souffrant de tyrosinémie de type I et réduit également le recours aux ressources en santé et à la greffe hépatique, diminuant ainsi les coûts associés.

Lion king or Aslan: a tale from Narnia!

In the Chronicles of Narnia series by C.S. Lewis, Aslan the all-powerful but benevolent lion does not need to have his tail twisted; rather, he twists tails to create convergence and harmony in his dream world. In this issue's lead article, "Twisting the Lion's Tail: Collaborative Health Policy Making in British Columbia," the authors discuss the problems regarding better coordination of health services research, knowledge translation and policy making. The roles of academia, health authorities and government are presently unclear, with leadership differences, power discrepancies, conflicting agendas, lag times and systemic structural complexity. Exploring these issues in British Columbia, Lindstrom, MacLeod and Levy advocate a change in perspective from practice gaps to bridging knowledge boundaries. Recommendations include networking of academia, action research and strengthening of relationships between stakeholders. However, a key cohesive element seems missing. Health technology assessment (HTA) is a formidable, dynamic driving force. With over 20 years' experience in HTA, Canada has a number of world-class innovative agencies federally and provincially that actively involve academia to generate evidence for informed policy making. Increased use of evidence-based medicine in research and the clinic may be achieved by augmenting HTA's scientific capacity through the creation of pan-Canadian exchange forums and by boosting the demand for knowledge translation.

Health technology assessment in Canada.

Canada's health system is a unique combination of public financing and private provision. With the significant government role in financing health services, health technology assessment (HTA) has found a ready audience as a form of policy research. In addition, Canada has been a leader in HTA and is entering a phase of deepening and maturation of HTA activities. The relative absence of dramatic change in the overall health system, coupled with public faith in the Canadian approach has been favorable to HTA's development in Canada. Emerging issues, beyond the demographic and economic pressures facing all Organisation for Economic Co-operation and Development health systems, include the convergence of assessment modalities and organizations for drug and nondrug technologies, increasing public concerns about the viability of Canada's approach to healthcare services, and the transition of HTA from an activity targeting macro-level policy makers to a management tool for healthcare facilities and providers.

The "natural history" of health technology assessment.

The collective experience of health technology assessment (HTA) in different countries delineates a pattern of development, a "natural history," of HTA in three phases: emergence, consolidation, and expansion. This study examines the rationale for HTA, definitions of its scope and breadth, its methods and organizational models, and its knowledge translation strategies, as HTA moves from one phase to the next. The study then identifies factors that facilitate or delay the transitions.

Health technology assessment: a review of international activity and examples of approaches with computed tomographic colonography.

The growth of health technology assessment (HTA) internationally is currently reflected in the growing membership of the International Network of Agencies for Health Technology Assessment. Many national and regional HTA institutions emerged in the 1980s and 1990s, and more recently, HTA has emerged in newly industrialized countries and in European Union member states in transition. Health technology assessment activities are becoming an increasingly important part of health care culture, with the appearance of HTA units in hospitals and hospital departments. This article provides a brief overview of who conducts HTA internationally and looks at how HTA is conducted and how this information is used. To highlight the different structures, processes, and methods available, a portion of this article is dedicated to describing different approaches that have been observed with respect to the assessment of computed tomographic colonography in North America for population-based colorectal cancer screening.

Assessing the performance of health technology assessment organizations: a framework.

In light of growing demands for public accountability, the broadening scope of health technology assessment organizations (HTAOs) activities and their increasing role in decision-making underscore the importance for them to demonstrate their performance. Based on Parson's social action theory, we propose a conceptual model that includes four functions an organization needs to balance to perform well: (i) goal attainment, (ii) production, (iii) adaptation to the environment, and (iv) culture and values maintenance. From a review of the HTA literature, we identify specific dimensions pertaining to the four functions and show how they relate to performance. We compare our model with evaluations reported in the scientific and gray literature to confirm its capacity to accommodate various evaluation designs, contexts of evaluation, and organizational models and perspectives. Our findings reveal the dimensions of performance most often assessed and other important ones that, hitherto, remain unexplored. The model provides a flexible and theoretically grounded tool to assess the performance of HTAOs.

The helix in the labyrinth: do we need genetic health services and policy research?

In Canada and elsewhere, targeted health services and policy research (HSPR) has been suggested as a means to clarify the health system implications of developments in genetics and genomics. But is such research really needed? We argue that substantial investments in basic genetic and genomic research, coupled with persistent uncertainty about the health system implications of advances in these fields, justify the development of specialized HSPR in genetics and the sustained involvement of the wider HSPR community. Genetic health services and policy research will play a crucial role in informing decision-makers at all levels of the health system about whether and how to integrate developments in genetics, genomics and other complex new technologies.

Expanding the scientific basis of health technology assessment: a research agenda for the next decade.

OBJECTIVES: The complexity of health technology assessment (HTA) has increased, in part because of its evolution through three distinct phases: the machine, the clinical outcomes, and the delivery models. However, the theoretical foundation for the field remains underdeveloped. METHODS: It is high time for HTA to bring together aspects of conceptual and theoretical works from other fields to strengthen the foundation of HTA. RESULTS: Many challenges await the further development of HTA. They can be captured around three research themes: adapting HTA to an evolving analysis object; translating HTA results into policy, management, and practice decisions; and evaluating organizational models of HTA. CONCLUSIONS: Consolidating the scientific basis of HTA is essential if we are to succeed in increasing the relevance of HTA in some of the most challenging health-related decisions that we will make as individuals and societies.

International Master's Program in health technology assessment and management: assessment of the first edition (2001--2003).

BACKGROUND: Despite a clear call for greater input from health technology assessment (HTA) in the areas of clinical practice and policy making, there are currently very few formal training programs. The objectives of our Consortium were to (i) develop a master's level program in HTA, (ii) test its content with a group of Canadian and European students, and (iii) evaluate the Program's strengths and weaknesses. OBJECTIVES: This study presents the results of our evaluation of the first edition of the Master's Program (2001--2003). METHODS: The evaluation relied on (i) a self-administered student questionnaire for each course (n = 142), (ii) interviews with students (n = 10), and (iii) interviews with internship supervisors (n = 5). RESULTS: A vast majority of students were satisfied with the course content and particularly appreciated the exercises and materials presented in an intensive format. However, they needed more systematic feedback from faculty members and recommended increasing the methodology content. The six key characteristics of the program are (i) flexible format adapted to the needs of skilled professionals, (ii) continuous interaction between HTA users and producers, (iii) international academic and professional collaboration, (iv) partnership with HTA agencies, (v) global approach to evidence-based methods and practices, and (vi) multidisciplinary approach. CONCLUSIONS: Despite the numerous organizational barriers inherent to creating an international program and several areas for improvement in the Program itself, the Ulysses Project was successful in attaining its objectives. Because there is a growing need for human resources with special training in HTA, further efforts need to be devoted to strengthening the international research capacity in HTA.

Determinants of discordance between patients and physicians in their assessment of lupus disease activity.

OBJECTIVE: We evaluated different methods for quantifying patient-physician discordance and identified factors associated with discordance in the assessment of lupus disease activity. METHODS: Data from 208 female patients who had a comprehensive annual examination were extracted from the Montreal General Hospital Lupus Registry. Discordance was measured by the difference between the patient self-reported 10 cm visual analog scale (VAS) and the physician VAS for global disease activity (VASDIFF). Multiple linear regression was used to identify the correlates of discordance, e.g., SF-36TM scales, Systemic Lupus Activity Measure (SLAM) components, etc. Four regression models were estimated using: (1) all patients; (2) only patients who evaluated disease activity higher than their physician's assessment; (3) only patients who evaluated disease activity lower than their physician's assessment; and (4) all patients, with the absolute value of VASDIFF as the dependent variable. RESULTS: Of the 208 observations, 150 (72%) of the VASDIFF scores were within +/- 2.5 cm on a 10 cm scale, indicating absence of marked discordance; 43 (20.7%) were from patients overscoring and 15 (7.2%) from patients underscoring their physician by at least 2.5 cm. Higher SF-36 role physical score, more bodily pain, and lower role emotional score in addition to the SLAM-skin component were independently associated with higher discordance. SF-36 social function and mental health scores as well as SLAM-neurological and kidney components were correlated with discordance in some subanalyses. Bodily pain was the most important variable for predicting "clinically relevant" discordance, followed by SLAM-skin and kidney components. CONCLUSION: Discordance between patients and physicians may result from patients scoring their disease activity based on their psychological and physical well-being, whereas physicians score disease activity based on the clinical and physical signs and symptoms of lupus.

Field triage of trauma patients: improving on the Prehospital Index.

The purpose of the present study was to evaluate the predictive ability of the Prehospital Index (PHI) in identifying injury severity and to develop a trauma triage scale that incorporates, along with the PHI, a subset of time independent variables to improve the predictive ability of the PHI-based triage instrument. This study included 1,291 trauma patients treated in Montreal, Canada. The developed trauma triage protocol was based on logistic regression analysis, in which the model that predicts the data best was selected by using Bayesian information criterion. The selected regression model included the variables age, body region injured, mechanism of injury, comorbidity, and PHI. This algorithm was a substantial improvement in detecting major versus non-major injuries (major injury defined based on death, intensive care unit admission, and surgery intervention) over the PHI alone (area under the receiver operating characteristic curve: 0.76 v 0.66, P <.05). Considering time independent variables could lead to better injury triage decisions.