David Grainger

Olanzapine vs risperidone in the management of schizophrenia: a randomized double-blind trial in Australia and New Zealand

Improved drug therapy for schizophrenia may represent the best strategy for reducing the costs of schizophrenia and the recurrent chronic course of the disease. Olanzapine and risperidone are atypical antipsychotic agents developed to meet this need. We report a multicenter, double-blind, parallel, 30-week study designed to compare the efficacy, safety, and associated resource use for olanzapine and risperidone in Australia and New Zealand. The study sample consisted of 65 patients who met DSM-IV criteria for schizophrenia, schizoaffective disorder, or schizophreniform disorder. Olanzapine-treated patients showed a significantly greater reduction in Positive and Negative Syndrome Scale (PANSS) total, Brief Psychiatric Rating Scale (BPRS) total, and PANSS General Psychopathology scores at endpoint compared to the risperidone-treated patients. Response rates through 30 weeks showed a significantly greater proportion of olanzapine-treated patients had achieved a 20% or greater improvement in their PANSS total score compared to risperidone-treated patients. Olanzapine and risperidone were equivalent in their improvement of PANSS positive and negative scores and Clinical Global Impression-Severity of Illness scale (CGI-S) at endpoint. Using generic and disease-specific measures of quality of life, olanzapine-treated patients showed significant within-group improvement in most measures, and significant differences were observed in favor of olanzapine over risperidone in Quality of Life Scale (QLS) Intrapsychic Foundation and Medical Outcomes Study Short Form 36-item instrument (SF-36) Role Functioning Limitations-Emotional subscale scores. Despite the relatively small sample size, our study suggests that olanzapine has a superior risk:benefit profile compared to risperidone.

Coverage with Evidence Development: Applications and issues

OBJECTIVES The aim of this study was to describe the current issues surrounding Coverage with Evidence Development (CED). CED is characterized by restricted coverage for a new technology in parallel with targeted research when the stated goal of the research or data collection is to provide definitive evidence for the clinical or cost-effectiveness impact of the new technology. METHODS Presented here is information summarized and interpreted from presentations and discussions at the 2008 Health Technology Assessment International (HTAi) meeting and additional information from the medical literature. This study describes the differences between CED and other conditional coverage agreements, provides a brief history of CED, describes real-world examples of CED, describes the areas of consensus between the stakeholders, discusses the areas for future negotiation between stakeholders, and proposes criteria to assist stakeholders in determining when CED could be appropriate. RESULTS Payers could interpret the evidence obtained from a CED program either positively or negatively, and a range of possible changes to the reimbursement status of the new technology may result. Striking an appropriate balance between the demands for prompt access to new technology and acknowledging that some degree of uncertainty will always exist is a critical challenge to the uptake of this innovative form of conditional coverage. CONCLUSIONS When used selectively for innovative procedures, pharmaceuticals, or devices in the appropriate disease areas, CED may provide patients access to promising medicines or technologies while data to minimize uncertainty are collected.

Comparative effectiveness research: the view from a pharmaceutical company.

Comparative effectiveness research (CER) represents the next stage in an evolution of research and knowledge development in regard to medical interventions. In this article we describe the challenges currently facing the innovative pharmaceuticals industry and briefly summarize the history of drug development, as context for the current movement to comparative effectiveness. CER should be considered alongside the wider field of health technology assessment (HTA), and we review the status of both CER and HTA internationally and their role in health policy. Limitations as to what can be achieved with HTA and limitations to the availability of evidence of comparative effectiveness at the time of market authorization provide ongoing challenges to all stakeholders. However, embracing CER is regarded as an essential step for the innovative pharmaceutical industry, as companies strive to more clearly demonstrate the effectiveness of their pipeline products with evidence that is compelling to payers and HTA agencies. Examples are given of how these evolving requirements from regulatory and HTA agencies are impacting on drug development efforts and how one company is responding. Finally, there are signs of increasing understanding and alignment across the various partners in drug development, registration and evaluation, and further suggestions are provided for consideration as the field matures and expands.

Economic Evaluation of Insulin Lispro versus Neutral (Regular) Insulin Therapy Using a Willingness-To-Pay Approach

SummaryThis willingness-to-pay (WTP) analysis is the first study of its kind undertaken in Australia to support an application for listing of a new drug on the Australian national formulary. The technique offers the advantage of being able to summarise diverse outcomes of therapy in a single unit of measure. Willingness to pay is used to value benefits in cost—benefit analysis (CBA), and CBA represents an absolute decision rule. An open—ended question with a bid—up approach was used to minimise bias and elicit the maximum amount patients would be willing to pay for insulin lispro. The WTP study incorporated scenarios describing the outcomes from insulin lispro and neutral (regular) insulin, the results from a formal metaanalysis and a description of the injection characteristics of the therapies. A sample of 83 patients with type I or II diabetes mellitus were surveyed using an open questionnaire to determine their maximum willingness to pay for the therapy they preferred. Overall, 92% of patients preferred insulin lispro (referred to as insulin A) and 8% preferred neutral insulin (referred to as insulin B). The incremental benefit per patient was calculated as 452.16 Australian dollars (

Clinical Outcomes with Insulin Lispro Compared with Human Regular Insulin: A Meta-analysis

A) per year.Insulin lispro was listed on the Australian national formulary at a 36% premium over neutral insulin, so the additional cost per patient would be

RELATIONSHIP BETWEEN FINANCIAL IMPACT AND COVERAGE OF DRUGS IN AUSTRALIA

A70.32 per year. Therefore, costs were exceeded by the benefits and insulin lispro was deemed to offer a net benefit. A multivariate analysis indicated that those patients who were middle—aged had the strongest preference for insulin lispro.

A Pilot Study to Identify Areas for Further Improvements in Patient and Public Involvement in Health Technology Assessments for Medicines

We performed a meta-analysis to compare insulin lispro and human regular insulin across a range of outcomes common in modern diabetes management to establish a basis for subsequent economic evaluation. We included all identifiable head-to-head randomized controlled trials, pooling dichotomous and continuous outcomes using appropriate statistical methods. Measures associated with various aspects of glycemic control (preparandial and postprandial glycemic control, glucose excursion, and glycated hemoglobin) and with hypoglycemia were evaluated. Results showed significant differences in favor of insulin lispro in the outcomes associated with postprandial glycemic control without an increase in hypoglycemia. Outcomes associated with fasting glycemic control and overall long-term glycemic control were not significantly different between insulin lispro and human regular insulin. Alternative approaches to the meta-analysis were explored but did not alter the conclusions. Thus our meta-analysis supports the existence of significant differences between insulin lispro and human regular insulin in terms of important postprandial outcome measures in diabetes. In addition, there is a practical difference in injection timing relative to meals: human regular insulin should be administered 30 to 45 minutes before eating, whereas insulin lispro can be administered 15 minutes or less before eating. These differences should be the subject of an economic evaluation to assist in determining the place of insulin lispro in diabetes management.

CAPACITY BUILDING IN AGENCIES FOR EFFICIENT AND EFFECTIVE HEALTH TECHNOLOGY ASSESSMENT

Objectives: The aim of this study was to estimate the relationship between the financial impact of a new drug and the recommendation for reimbursement by the Australian Pharmaceutical Benefits Advisory Committee (PBAC). Methods: Data in the PBAC summary database were abstracted for decisions made between July 2005 and November 2009. Financial impact—the upper bound of the values presented in the PBAC summary database—was categorized as ≤A

IS THIS THE REAL LIFE? IS THIS JUST FANTASY?

0, >A

Patient Involvement in Medicine Development and Assessment

0 up to A