INTRODUCTION

HISTORY

In 1972, Archie Cochrane advocated the randomized clinical trial to promote higher-quality medical evidence.1 But it was not until the last decade of the 20th century that the term “evidence-based medicine” came into vogue.2,3 Evidence-based medicine is essentially what the name implies – the practice of medicine based upon the highest-quality and most reproducible evidence available.

More recently, the term “value-based medicine” has been introduced into health care by our group of researchers at the Center for ValueBased Medicine.5–8 Value-based medicine incorporates the highest level of evidence-based medicine and takes it to a higher level by incorporating patient-based quality-of-life preferences to measure the value conferred by an intervention. This value is then amalgamated with the resources expended upon an intervention to produce a cost–utility ratio. Value and cost–utility ratio are the most important measures in value-based medicine. As the reader will see, value-based medicine allows a quality of health care heretofore not possible.

This article will briefly discuss evidence-based medicine and then elaborate on the various forms of pharmacoeconomic analyses. The last of the pharmacoeconomic analyses is cost–utility analysis, the most sophisticated variant and the foundation for value-based medicine. Value-based medicine pharmacoeconomic analyses standardize the input variables used in cost–utility analysis to allow a comparison of comparative effectiveness (value) and cost-effectiveness of a drug across all specialties in medicine.

KEY CONCEPTS

EVIDENCE-BASED MEDICINE

There are essentially five levels of medical interventional evidence.4 The higher the level, the greater the confidence the clinician can have that the information is reproducible (reliable).

The highest level of evidence, level 1, is that supplied by the randomized clinical trial with low type 1 and type 2 errors. This means a P- value of <0.05, and a β of <0.20, or a power (1 − β) of 80% or more to detect a predetermined difference among groups. Level 2 evidence is supplied by the randomized clinical trial with a type 1 error >0.05 and/ or a type 2 error >0.20. Level 3 evidence occurs with a nonrandomized clinical trial, while the case series provides level 4 evidence and the case report provides level 5, or anecdotal evidence. A summary of the levels of interventional evidence is shown in Table 52.1.4

In addition to the level of evidence, the clinician should also be cognizant of whether a study is properly masked and has an acceptable dropout rate.2 Masking can occur in the form of a single-blind study in which a patient typically does not know which treatment is being given, and the double-blind study, in which neither the researcher nor the

patient knows which treatment is being given. A double-blinded study is preferable, but may not always be possible.

A dropout rate of <5% is considered excellent, while a rate of 5–15% is acceptable and a rate greater than 20% casts suspicion upon the validity of a study.2 For example, a 10% event rate can be misleading if there is a 30% dropout rate and half of those who dropped out (15% of all participants) also had an event. Thus, the true event rate might have been 25%, or 250% higher than found in the study with a 30% dropout rate. An intent-to-treat study keeps in all patients who are randomized,2 thereby allowing the reader to know the dropout rate. Importantly, the quality of evidence incorporated into a pharmacoeconomic analysis is only as strong as its weakest link.

Lastly, the reader should be aware of the terms “criterion validity” and “construct validity.” Criterion validity measures how well an intervention measures up to a criterion, or “gold standard.” For example, how does a new drug for the treatment for neovascular macular degeneration measure up to the gold standard of vascular endothelial growth factor (VEGF) inhibitors? Construct validity assesses how effectively something measures what it is supposed to measure. For example, how well does the quality-of-life instrument National Eye Institute Visual Functioning Questionnaire 25 (NEI-VFQ-25)9 for ocular diseases actually measure the quality of life associated with neovascular macular degeneration?5,10

TYPES OF PHARMACOECONOMIC ANALYSIS

There are essentially four types of pharmacoeconomic analyses. In order of increasing complexity, these are: (1) cost minimization analysis;

(2) cost–benefit analysis; (3) cost-effectiveness analysis; and (4) cost– utility analysis.5,10

COST MINIMIZATION ANALYSIS

Cost minimization analysis compares the cost of two similar inter­ ventions to ascertain which is less expensive. Cost minimization analysis, however, suffers from the problem that it often compares two different interventions that may initially seem similar but are not. For example, two VEGF inhibitors for the treatment of neovascular age-related macular degeneration (AMD) may have similar visual results. Nonetheless, the types of adverse events associated with each may differ very significantly, as may the incidence of each of the adverse events. Thus, even though they may superficially seem very similar, the drugs are often not exactly comparable. Thus, this form of analysis is used infrequently today.

An example of a reasonable cost minimization analysis would be one that compares the administration of the same VEGF inhibitor, with the same administration technique, in the hospital outpatient setting versus that in a private office. Here the exact same intervention is performed in a different setting and the cost is compared to ascertain which is less expensive.