The clinical trials submitted for review to the FDA by the manufacturer determine the indications for which a drug may be marketed. Although trials used to obtain approval may be sufficient to convince regulatory authorities that a new drug is safe and effective, their design may or may not be adequate to convince health care payers that a new drug represents a therapeutic advance over existing therapies. Therefore, trial design from first toxicology testing to pivotal trials and post-marketing studies is of paramount importance in affecting future drug utilization.
Numerous factors influence which drugs manufacturers choose to develop, and for which particular indications:
- Market competition or saturation;
- In-house clinical expertise and infrastructure;
- Potential market size and patient recruitment potential; and
- Reimbursement status of target population.
In general, manufacturers express no bias against developing a new drug for mental health indications in comparison with physical health indications. One manufacturer did mention that because most behavioral health users have public health insurance, patient recruitment and retention could be a greater challenge for behavioral health than for physical health drugs. This could be especially true in non-institutionalized schizophrenia patients, for example. Similarly, if a product demonstrates potential for both mental health and physical health indications, a lack of clinical expertise in mental health may lead the manufacturer to pursue the physical health indication. In general, manufacturers do not design trials for specific racial/ethnic groups or special populations (e.g., children) unless requested to do so by the FDA.
The MCOs and PBMs interviewed reported that traditional clinical trials are of relatively short duration and measure outcomes using instruments not readily translatable into regular clinical practice, such as standardized psychiatric rating scales. As a result, many manufacturers conduct outcomes studies that measure clinical, quality of life and/or economic endpoints. The respondents interviewed in this study indicated that in order to speed formulary acceptance, manufacturers should:
- Complete head-to-head comparisons with competing agents;
- Conduct long-term trials;
- Conduct real world effectiveness trials in naturalistic settings; and
- Include measures of "big picture" issues such as employee productivity.
Some health care payers are beginning to standardize their operating procedures for the review of new agents. For example, Regence BlueShield (Seattle, WA)39 and Blue Cross/Blue Shield of Colorado and Nevada40 have published guidelines for the submission of clinical and economic data supporting formulary consideration.
Manufacturers are responding to the request for such studies. We are aware of numerous outcomes studies of this type for both antidepressants and antipsychotics. Eli Lilly has conducted two direct comparisons of olanzapine and risperidone.41 Janssen is conducting a comparison of outcomes in patients treated with risperidone to those achieved in patients treated with one of 13 different conventional antipsychotics (this trial is named the ROSE trial). Often, payers are conducting this work themselves. For example, Group Health of Puget Sound conducted a comparison of the efficacy and cost-effectiveness of SSRIs to TCAs in a naturalistic, primary care setting.42