CORTICOID, VEHICLE, AND SKIN INTERACTION Table II Performance of Lidex© • (0.05% Fluocinonide in FAPG ©,• Cr3am) in Treatment of Psoriasis in 242 Subjects 587 Study A Study B Study C Tot,l Lidex Compared to W/L/T o W/L/T W/L/T W/L/T Placebo 13/1/lc 13/1 Hydrocortisone 0.5% 10/0/3c 70/12/20• 80/12/23 Betamethasone valerate 0.1% 7/5/18 47/6/29c 54/11/47 a Syntex Laboratories, Inc., Palo Alto, Calif. 0 W denotes greater improvement with Lidex, L denotes greater improvement with com- parative material, T denotes no difference. ß Statistically significantp 0.01. Figure 10 shows one of many psoriasis cases which have benefited from our efforts. A major point to remember is that topical corticoids, such as hydrocortisone, had been unable to significantly influence this disease until the advent of their fiuorinated derivatives. These compounds were particularly effective in psoriasis when used under occlusive dressings. With the development of fiuocinonide and properly designed vehicles, the same dramatic results can now often be achieved without occlusive dressings. Analysis Sequential analysis has recently been utilized to scrutinize results as they become available and allows termination of the trial as soon as sta- tistical significance is reached (39). In fact, however, we frequently con- tinue gathering case reports so that we can better evaluate drug safety. CONCLUSION A long and increasingly difficult path must be followed in the devel- opment of new, effective medications. We have outlined just some of the steps which are followed in our research and development labora- tories during the creation of new topical corticoids (4'0). It is certainly a far cry from the early days where a new chemical moiety was pulverized and incorporated into a nice, white cream which was the favorite of the production supervisor. We have not even touched upon the many ana- lytical problems inherent in establishing the chemical integrity of minute concentrations of these increasingly sophisticated molecules in unusual and complex vehicles, as well as in the media of our release and penetra- tion studies. Nor have we touched upon vehicle aesthetics, packaging stability, and preservation problems which would have been our prime

588 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Figure 10. Lidex (fiuocinonide) Cream 0.05% effective adjunctive therapy in psoriasis. Male, age 5•, psoriasis of 8 years' duration before (top) and after (bottom) •5 days' treatment with Lidex Cream 0.05% q.i.d. without occlusion