Publications

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.

Although CXCR4-tropic viruses are relatively uncommon among untreated human immunodeficiency virus (HIV)-infected individuals except during advanced immunodeficiency, the prevalence of CXCR4-tropic viruses among treated patients with detectable viremia is unknown. To address this issue, viral coreceptor usage was measured with a single-cycle recombinant-virus phenotypic entry assay in treatment-naive and treated HIV-infected participants with detectable viremia sampled from 2 clinic-based cohorts. Of 182 treated participants, 75 (41%) harbored dual/mixed or X4-tropic viruses, compared with 178 (18%) of the 976 treatment-naive participants (P<.001). This difference remained significant after adjustment for CD4+ T cell count and CCR5 Delta 32 genotype. Enrichment for dual/mixed/X4-tropic viruses among treated participants was largely but incompletely explained by lower pretreatment nadir CD4 + T cell counts. CCR5 inhibitors may thus be best strategically used before salvage therapy and before significant CD4 + T cell depletion.