Novel approaches to incorporating pharmacoeconomic studies into phase III clinical trials for Alzheimer's disease

Abstract

The societal and individual costs of Alzheimer's disease are significant, worldwide. As the world ages, these costs are increasing rapidly, while health systems face finite budgets. As a result, many regulators and payers will require or at least consider phase III cost-effectiveness data (in addition to safety and efficacy data) for drug approval and reimbursement, increasing the risks and costs of drug development. Incorporating pharmacoeconomic studies in phase III clinical trials for Alzheimer's disease presents a number of challenges. We propose several specific suggestions to improve the design of pharmacoeconomic studies in phase III clinical trials. We propose that acute episodes of care are key outcome measures for pharmacoeconomic studies. To improve the possibility of detecting a pharmacoeconomic impact in phase III, we suggest several strategies including; study designs for enrichment of pharmacoeconomic outcomes that include co-morbidity of patients; reducing variability of care that can affect pharmacoeconomic outcomes through standardized care management; employing administrative claims data to better capture meaningful pharmacoeconomic data; and extending clinical trials in open label follow-up periods in which pharmacoeconomic data are captured electronically by administrative claims. Specific aspects of power analysis for pharmacoeconomic studies are presented. The particular pharmacoeconomic challenges caused by the use of biomarkers in clinical trials, the increasing use of multinational studies, and the pharmacoeconomic challenges presented by biologicals in development for Alzheimer's disease are discussed. In summary, since we are entering an era in which pharmacoeconomic studies will be essential in drug development for supporting regulatory approval, payor reimbursement and integration of new therapies into clinical care, we must consider the design and incorporation of pharmacoeconomic studies in phase III clinical trials more seriously and more creatively.

Medicare Expenditures of Individuals with Alzheimer's Disease and Related Dementias or Mild Cognitive Impairment Before and After Diagnosis

“…Furthermore, Medicare alternative payment models, such as bundled payment for episodes of care and person‐centered medical homes, that provide care for individuals with ADRD and MCI will need to address care transitions explicitly across settings and over time . For example, episode‐based payments may include emergency department visits, hospitalization, postacute SNF care, and home health services related to the acute event . Unlike fee‐for‐service reimbursement, bundled payment approaches that combine payment for multiple services that individuals receive during an episode of care provide incentives to deliver healthcare services more efficiently while improving care quality …”

“…34,35 For example, episode-based payments may include emergency department visits, hospitalization, postacute SNF care, and home health services related to the acute event. 37 Unlike fee-for-service reimbursement, bundled payment approaches that combine payment for multiple services that individuals receive during an episode of care provide incentives to deliver healthcare services more efficiently while improving care quality. 38 Clinical studies suggest that, although not every individual with MCI progresses to AD they are at greater risk; as many as 15% may develop ADRD each year.…”

Exploring the Relationship between Alzheimer's Disease Severity and Longitudinal Costs

“…This review shows that most articles had important sample limitations: only six articles had large sample sizes (Ͼ1000), and only five articles used longitudinal data. These sample limitations can be important, because reduced sample size and shortened time of the study reduce the probability of observing meaningful pharmacoeconomic outcome [9]. The AD severity information provided in most published articles was not comprehensive.…”

“…There is need for a comprehensive assessment of direct and indirect resources utilization and for research with a greater level of evidence regarding the relationship between AD severity and costs [9]. The objective of this article was to improve estimation of the relationship between changes in AD severity measures and costs of care by using more comprehensive data and improved statistical methodologies.…”

Editorial

“…Among many interesting findings and suggestions, three main conclusions emerge from that special issue (23)(24)(25)(26)(27)(28)(29)(30), which bring guidance for future research on the health economics of AD. New creative pharmacoeconomics models are needed.…”