Perhaps the most fundamental driver of pharmaceutical utilization is the clinical trial history of a particular drug. A pharmaceutical is approved for use by the FDA for a particular indication based on the clinical trials submitted by the manufacturer. The labeling therefore reflects only the evidence presented by the manufacturer in the filing. A drug may be effective in many more indications than that for which it is approved for marketing by the FDA. Examples include fluvoxamine, an SSRI approved for marketing in the US only for the treatment of Obsessive-Compulsive Disorder, although it is widely used as an antidepressant in Europe. Similarly, atypical antipsychotics are used with some frequency for the treatment of bipolar disorder and the treatment of behavioral disturbances in dementia patients, even though these medications are only approved for use in schizophrenia and related illnesses. Health care payers are therefore often placed in a difficult situation: is it proper to reimburse a drug used to treat an indication for which it is not approved, even if such use is commonplace?
Post-approval, pharmaceutical marketing plays an important role in influencing physician and consumer awareness of current therapies. This influence comes partially through physician education: pharmaceutical representatives distribute literature (approved by the FDA) documenting the appropriate use and efficacy of the agents they represent. In addition, the industry sponsors numerous physician education symposia and programs that qualify for continuing medical education (CME) credit either at a local level or at national meetings. Furthermore, marketing to physicians often involves the distribution of pharmaceutical samples, the availability of which may have an influence on which agent within a particular class of similar drugs is chosen by the physician for an individual patient. In 1997, the pharmaceutical industry spent approximately $7.0 billion on marketing (i.e. "detailing") to health care professionals.14 In addition to direct detailing of health care professionals, the pharmaceutical industry places advertisements in clinical and trade journals to promote products. Recently, antidepressants have led other classes of drugs in spending for journal-based advertising. In 1999, citalopram, the antidepressant co-marketed by Forest and Parke-Davis, was the most-advertised product in this class, followed closely by Eli Lilly's fluoxetine.15
In recent years, Direct-to-Consumer (DTC) marketing has become more prevalent. The 10 drugs most heavily advertised to consumers in 1998 accounted for $9.3 billion (or approximately 22%) of the total increase in drug spending between 1993 and 1998.16 During the first 10 months of 1998, pharmaceutical companies spent $1.1 billion on DTC ads, compared with $1.0 billion in 1997. The only psychotherapeutic entering the top five drugs in DTC spending was Glaxo Wellcome's Zyban, a version of bupropion approved as a smoking-cessation aid, that totaled $5.7 million in advertising expenditures.17