Comparative effectiveness research and genomic personalized medicine.

Abstract

What is comparative effectiveness research? Although healthcare expenditures continue to rise rapidly in the USA, clinical measures of the health of the population have fallen behind many other developed countries. As shown in Figure 1, the average US healthcare expenditures have grown more rapidly over the past 30 years than in any other major industrialized country. Cancer treatments constitute a substantial proportion of these escalating costs, with novel biologic agents constituting an ever greater share [1]. Even more distressing is evidence that outcomes achieved from that healthcare spending, including life expectancy, are poor compared with health outcomes in other industrialized nations. (Figure 2) [2]. To address this challenging environment, it is essential to identify important diagnostic and therapeutic questions, and to acquire, evaluate and, where appropriate, synthesize all relevant information related to effectiveness, safety and overall value of comparative diagnostic, treatment and prevention strategies in order to properly inform important clinical and policy decisions. Comparative effectiveness research (CER) attempts to frame the delivery of healthcare by contrasting the benefits and harms of different diagnostic, therapeutic or preventative strategies in typical patients in an effort to define the most effective, safe and efficient interventions. The Institute of Medicine (Washington, DC, USA) defines CER as [3]: “...the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat and monitor a clinical condition, or to improve the delivery of care. The purpose of comparative effectiveness research is to assist consumers, clinicians, purchasers and policy-makers to make informed decisions that will improve healthcare at both the individual and population levels.” Fundamental to this definition is the direct comparison of the effectiveness and safety of different interventions in ‘typical’ patients seen in everyday practice. Comparative results from prospective randomized controlled clinical trials (RCTs) or systematic reviews of such trials represent the ‘gold standard’ of CER. Since RCTs may be of poor quality, not available or sometimes even unethical and, at best, based on highly selected patients not representative of the general population, alternative sources of evidence are often utilized to guide the evaluation of new interventions and address the need for patients, clinicians and policy-makers to make critical decisions. The limitations of available evidence from RCTs have led to the exploration of additional sources, which, when applied with the same rigorous attention to study design, conduct, ana lysis and reporting, may provide reasonable, valid and generalizable estimates of comparative effectiveness, safety and costs (Box 1). Such approaches include carefully conducted cohort and population studies, as well as clinical simulations utilizing evidence from RCTs, meta-analyses, cohort and population studies to emulate realistic clinical scenarios reflecting the impact of an intervention on clinical effectiveness, toxicity, quality of life and costs. The ultimate goal of CER is to gather the totality of available evidence to address the comparative effectiveness, toxicity and overall value of established and emerging interventions.