The term "cost-effectiveness" has been broadly applied to several methods of pharmacoeconomic analysis which compare the clinical and/or quality of life outcomes and costs associated with competing pharmacological agents. Measurements used in pharmacoeconomic analyses of the newer psychotropic therapies include cost-of-illness, cost-minimization, cost-effectiveness, cost-benefit, and cost-utility. The principal difference among these types of analyses are outlined in Exhibit VII-1 below.
In addition to differences in analysis strategy, pharmacoeconomic studies vary by method of data collection. Although stand-alone medical outcomes or economic measurements collected during randomized clinical trials (i.e., "piggyback" trials) are the "gold-standard" for pharmacoeconomic analyses, these are expensive to conduct and have not been widely implemented in the study of mental health. Retrospective or prospective medical claims analysis and decision-analytic economic models are far more common.59
Exhibit VII-1. Comparison of Pharmacoeconomic Methodologies
|Cost-of-illness||Examines all direct and indirect costs of an illness to a population|
|Cost-minimization||Assumes equivalent outcomes and compares costs of treatment to determine which is least costly|
|Cost-effectiveness||Compares the costs of treatments with the health benefits derived; frequently addresses cost optimization more than reduction (measures marginal cost per unit of improved outcome)|
|Cost-benefit||Converts all costs, benefits, and negative effects to monetary units ($) to determine which treatment has the lowest cost-to-benefit ratio|
|Cost-utility||Applies preferences values to outcomes in cost-effectiveness studies; examines effects on length and quality of life, using such outcomes as the quality-adjusted life-year (QALY)|
Adapted from Conner et al 1999.44
To date, few well-designed pharmacoeconomic studies have been conducted to evaluate the cost-effectiveness of the newer antipsychotic and antidepressant medications compared to conventional therapies. Although experts emphasize the superiority of large-scale, prospective, comparative studies in pharmacoeconomic evaluation,59 the majority of studies use less reliable, and perhaps more convenient methods of economic analysis.
Analysis of claims from a health care payer can take one of several approaches. If the comparison groups are used concurrently in clinical practice, it may be possible to identify patients who have taken either therapy and analyze average costs between treatment groups. The majority of economic studies to date in the literature are uncontrolled retrospective historical analyses which estimate cost-savings for competing treatments. In these studies the researchers examine the costs of treatment (and other outcomes) one year prior to and one to two years following treatment with the study medication. In the pre-study phase, patients may have been treated with one of several therapeutic strategies. For this reason, such studies lack a true control group, making it difficult to attribute cost and clinical outcomes to a specific course of therapy.
Decision-analytic models are a convenient tool to estimate the true cost-effectiveness of treatment over a lifetime. However, these models rely heavily on clinical and economic assumptions because good evidence on lifetime costs and utilities are not currently available.53 Sensitivity analyses that adjust the clinical and economic outcomes probabilities are essential to demonstrating the validity of these models. This is especially true when one outcome parameter may be ill-defined or where these parameters may be obtained from studies that are not strictly applicable to a real-world setting.
Until the mid to late 1990's, retrospective, often uncontrolled, historical analyses were most common in evaluating cost-effectiveness of newer antipsychotics, whereas retrospective reviews of health care payer claims were most common for evaluating cost-effectiveness of newer antidepressants. A small number of large-scale real-world effectiveness trials have recently been conducted or are currently in progress for both antidepressants and antipsychotics.
In the 13 years since the initial launch of bupropion in the United States, physicians and patients have rapidly adopted new-generation antidepressant and antipsychotic medications as first-line treatments for depressive and psychotic illnesses. These new agents have provided treatment alternatives to established therapies such as the tricyclic antidepressants (TCAs) and the typical antipsychotics that had been in use for more than two decades. These new agents have also brought with them price tags that are substantially larger than those associated with the agents they hoped to replace.
Although it has been broadly assumed in the popular understanding that new generation antidepressant and antipsychotic medications are more effective than the older generations, the argument for their use, based on efficacy alone, is far from clear. A recent meta-analysis of antidepressant agents published by the Agency for Health Care Policy and Research concluded that SSRIs and other new-generation antidepressants are no more effective than TCAs.60 As a result, the rationale for the use of these newer (and more expensive) agents has rested on arguments surrounding ease of use, tolerability, general safety, safety in overdose (i.e., easy of suicide attempts), and (perhaps consequently) net cost-savings to the total health care system. Indeed, Hylan and coworkers warn that compliance with therapy by a patient depends on the particular pharmaceutical used itself, and therefore assuming equal efficacy as a result of equal use is not tenable.48