Designing and conducting psoriasis clinical trials is tricky. After all, psoriasis is a highly variable group of conditions that produce a range of debilitating and often subjective symptoms. So how do researchers assess efficacy in novel psoriasis treatments? Read on for the answer.
Considerations for Psoriasis Trials
In clinical practice, broad global assessments are used to determine disease severity as well as effectiveness of psoriasis treatment. However, when conducting trials, more objective and clinically meaningful metrics are needed. To determine clinical efficacy for market approval, researchers must be able to directly compare novel therapies with current treatment regimens. As such, most clinical trials focus on objective physical measures of efficacy for clinical endpoints with quality of life assessments as secondary, but still important.
Psoriasis Trial Efficacy Endpoints
There are generally two major efficacy endpoints used in psoriasis clinical trials: the Investigator’s Global Assessment (IGA) scale and the Psoriasis and Severity Index (PASI). In particular, trials involving oral or biologic therapies typically use both IGA and PASI as co-primary endpoints for response rates.
The IGA was originally developed with input from both clinical investigators and regulatory authorities. It’s a tool that’s not just used in psoriasis research; the IGA is the most valued endpoint for the FDA for almost all dermatological study indications, including acne and eczema. The IGA is typically the primary endpoint for topical psoriasis treatments.
The IGA scale is a visual assessment that consists of a score ranging from 0 (clear) to 4 (severe). Skin rated a 4 is bright red in color with marked plaque elevation and is dominated by thick, non-tenacious scale. For a treatment to be considered successful, the affected area must receive a score of 0 or 1 and experience a two-point improvement from baseline.
The PASI is a metric especially important for systemic therapies. In this assessment, a patient’s skin is mapped out as four major areas: head, arms, trunk, and legs. Like the IGA, the PASI is graded on a five-point severity scale. However, erythema, induration, and desquamation are all evaluated independently. The PASI also includes a rough percentage of the area of skin affected with a seven-point grading system. The PASI has been adapted for use in trials involving other skin disorders, including eczema and vitiligo.
Another useful tool is the Dermatology Life Quality Index (DLQI). Originally developed in 1994 as the first dermatology-specific quality-of-life metric, the DLQI consists of a simple survey with 10 questions. Since then, this assessment has been used for over 40 different skin conditions in 80 countries. It’s also become the most widely used quality-of-life metric in psoriasis trials today. Interestingly, correlation between DLQI and PASI scores are not always high. However, a recent comprehensive review found that mean DLQI and PASI do correlate predictably among patients with chronic, moderate-to-severe plaque psoriasis undergoing treatment with biologics.
Psoriasis Trial Design Strategies
IGA and PASI are tools that rely entirely on visual assessment and, because psoriasis is generally symmetrical, left/right studies (also called self-control studies) can be effective means of achieving proof of concept during early treatment development. One arm or leg receives the investigative drug, while the other receives the vehicle. This requires less than half the number of individuals necessary to achieve the statistical power compared to a traditional inter-individual study. Disadvantages include occasional patient confusion in regards to left vs. right or the deliberate use of only one topical on both sides. The FDA only allows intra-individual left/right studies in early Phase II studies; Phase IIb and Phase III studies must utilize inter-individual methods.
If you’d like to know more about designing and conducting psoriasis clinical trials, our latest dermatology webinar may give you some useful insights.