For each of the case studies, we used several different kinds of sources to collect information on the market barriers to the development of each drug. For each case study, we conducted a thorough literature search, including peer-reviewed sources, and the gray literature. The information gathered from print materials was supplemented with interviews of key individuals from industry and government who were involved in the development, evaluation, and commercialization of the product.
The literature review was conducted by a direct search of MEDLARS databases, including MEDLINE (citations of peer-reviewed journal literature), HealthSTAR (citations of journal literature and other sources in health services research, technology assessment, and health planning), and HSRProj (citations of recent and ongoing health services research funded by government and the private sector). Among the bibliographic databases, we focused in particular on MEDLINE 1966 - present and HealthSTAR 1984 - present to obtain information on clinical trials, product development and marketing. It was critical to examine articles that dated back to the 1960's for all of the case studies, as some of the early preclinical and clinical development happened well over thirty years ago. The search was restricted to English-language publications particularly because we were focusing on issues related to market barriers in the US. In addition, a similar search was conducted in Dialog databases which compiles journal articles from a variety of database sources including Scrips, ABI/INFORM ®, FDA Pink Sheet, and IAC Trade and Industry Database. The MeSH (Medical Subject Headings) terms used to identify articles for the LAAM, naltrexone, clozapine, and Nicorette case studies are shown in Appendix C.
To identify articles pertinent to the development of LAAM, the search strategy included both LAAM and methadone, a medication currently used by all opioid treatment programs for maintenance therapy. The use of methadone in the search facilitated the discovery of articles that compared the two medications.
For naltrexone, the search strategy included both NALTREXONE, the generic name of the product, and TREXAN, the trade-name of the product for the opioid indication. The use of TREXAN as part of the search strategy effectively reduced the scope of the literature search to the key opioid indication, as many disparate research projects were published using naltrexone, unsuccessfully to treat a variety of other conditions. Since naltrexone is currently indicated for the treatment of two conditions (opioid addiction and alcoholism), our literature review encompassed the key issues to the development of naltrexone for both indications.
For the other two case studies, MeSH terms for CLOZAPINE and SCHIZOPHRENIA were used to identify articles on clozapine, and MeSH terms for Nicorette and smoking cessation therapy were used to identify articles on Nicorette. Nicotine polacrilex (the generic name for Nicorette) was also used in our search strategy for Nicorette, and proved useful in gathering articles on the compound's marketing.