Publications

OBJECTIVES

We explored whether the United States, which does not regulate pharmaceutical prices, is responsible for the development of a disproportionate share of the new molecular entities (NMEs; a drug that does not contain an active moiety previously approved by the Food and Drug Administration) produced worldwide.

METHODS

We collected data on NMEs approved between 1992 and 2004 and assigned each NME to an inventor country. We examined the relation between the proportion of total NMEs developed in each country and the proportion of total prescription drug spending and gross domestic product (GDP) of each country represented.

RESULTS

The United States accounted for 42% of prescription drug spending and 40% of the total GDP among innovator countries and was responsible for the development of 43.7% of the NMEs. The United Kingdom, Switzerland, and a few other countries innovated proportionally more than their contribution to GDP or prescription drug spending, whereas Japan, South Korea, and a few other countries innovated less.

CONCLUSIONS

Higher prescription drug spending in the United States does not disproportionately privilege domestic innovation, and many countries with drug price regulation were significant contributors to pharmaceutical innovation.

Previous work has suggested that an extracellular matrix degrading enzyme-matrix metalloproteinase-2 (MMP-2) plays an important role in the development of muscle atrophy. However, the transcriptional regulation mechanism of MMP-2 in skeletal muscle atrophy remains largely unknown. Using transgenic MMP-2 promoter reporter mice, we have demonstrated that AP-1 and RE-1 binding sites in the MMP-2 promoter region, coupled with increased binding of Fra-1, Fra-2 and AP-2, play a critical role in MMP-2 transcriptional regulation in muscle atrophy. Novel information gained from this study has improved our understanding of in vivo transcriptional regulation of MMP-2 in skeletal muscle atrophy.

BACKGROUND & AIMS

Cirrhosis is a prevalent and expensive condition. With an increasing emphasis on quality in health care and recognition of inconsistencies in the management of patients with cirrhosis, we established a set of explicit quality indicators (QIs) for their treatment.

METHODS

We organized an 11-member, multidisciplinary expert panel and followed modified Delphi methods to systematically identify a set of QIs for cirrhosis. We provided the panel with a report that summarized the results of a comprehensive literature review of data linking candidate QIs to outcomes. The panel performed independent ratings of each candidate QI by using a standard 9-point RAND appropriateness scale (RAS) (ranging from 1 = not appropriate to 9 = most appropriate). The panel members then met, reviewed the ratings, and voted again by using an iterative process of discussion. The final set of QIs was selected; QIs had a median RAS >7, and panel members agreed on those selected.

RESULTS

Among 169 candidate QIs, the panel rated 41 QIs as valid measures of quality care. The selected QIs cover 6 domains of care including ascites (13 QIs), variceal bleeding (18 QIs), hepatic encephalopathy (4 QIs), hepatocellular cancer (1 QI), liver transplantation (2 QIs), and general cirrhosis care (3 QIs). Content coverage included prevention, diagnosis, treatment, timeliness, and follow-up.

CONCLUSIONS

We developed an explicit set of evidence-based QIs for treatment of cirrhosis. These provide physicians and institutions with a tool to identify processes amenable to quality improvement. This tool is intended to be applicable in any setting where care for patients with cirrhosis is provided.