Publications

A pan-viral DNA microarray, the Virochip (University of California, San Francisco), was used to detect human parainfluenzavirus 4 (HPIV-4) infection in an immunocompetent adult presenting with a life-threatening acute respiratory illness. The virus was identified in an endotracheal aspirate specimen, and the microarray results were confirmed by specific polymerase chain reaction and serological analysis for HPIV-4. Conventional clinical laboratory testing using an extensive panel of microbiological tests failed to yield a diagnosis. This case suggests that the potential severity of disease caused by HPIV-4 in adults may be greater than previously appreciated and illustrates the clinical utility of a microarray for broad-based viral pathogen screening.

A disintegrin and metalloprotease 33 (ADAM33) is a transmembrane protease and integrin ligand that has been identified as an asthma susceptibility gene product. To determine whether ADAM33 plays important roles in mammalian development and the modulation of allergic airway dysfunction, we generated ADAM33-null mice by gene targeting. ADAM33-null mice were born at expected Mendelian ratios, and both male and females developed normally and were fertile. No anatomical or histological abnormalities were detected in any tissues. In an animal model of allergic asthma, ADAM33-null mice showed normal allergen-induced airway hyperreactivity, immunoglobulin E production, mucus metaplasia, and airway inflammation. Our results demonstrate that ADAM33 is not essential for growth or reproduction in the mouse and does not modulate baseline or allergen-induced airway responsiveness.

PURPOSE OF REVIEW

The purpose of this review is to discuss the challenges inherent in the design of clinical trials for patients with systemic lupus erythematosus.

RECENT FINDINGS

Recent years have witnessed a renewed interest in the conduct of systemic lupus erythematosus clinical trials. Three key design decisions play particularly critical roles in determining the fate of these trials: selection of the study population from among patients with very heterogeneous disease manifestations; selection of the treatment and control regimens; and selection of the primary endpoint. Four recent randomized, controlled trials dealt with these decisions in the context of a variety of interventions, including new biologic agents, hormonal therapies, and anti-metabolites. These trials are informative about the implications of each approach.

SUMMARY

Systemic lupus erythematosus investigators are faced with substantial trial design challenges because of the inherently complex nature of this disease. The hope is that lessons learned from prior and ongoing trials will inform future trial design such that the efficacy of new agents can be determined and new therapies will become available for patients with SLE.

Increasing knowledge of the genetic basis of disease is changing the landscape of health care. Two critical aspects are growth in biotechnology and growth in personalized health care, particularly targeting medicines based on genetic information (pharmacogenomics). This paper provides an overview of the health policy implications of the integration of biotechnology and pharmacogenomics. I examine four factors that determine whether relevant technologies will be successfully adopted, using case studies for illustration. Key policy challenges include determining the appropriate role of policy in (1) providing incentives to develop socially beneficial interventions and (2) facilitating development of the evidence base.

Biotechnology has figured prominently in recent Medicare coverage and payment policies. Biotech treatments push policy boundaries for several reasons: They attract strong patient demand; they often treat rare or life-threatening diseases; they may have uncertain evidence of health benefits; and they are often costly. This paper considers case studies of Medicare coverage for off-label uses of biotech cancer drugs and payments for anemia biopharmaceuticals. The cases suggest Medicare's ongoing challenge to balance access considerations, the role and strength of evidence, and cost consequences of new treatments.