Data in dermatological clinical trials are prone to subjectivity, and therefore, vulnerable to inaccurate conclusions. This subjectivity problem occurs mainly due to human inconsistencies when making crucial assessments of lesions by using photography, or estimating measures on subjective scales that analyze color, shape, or border irregularity. These assessments can be difficult, even for a trained dermatologist.
 
A study from the JAMA Dermatology has shown that not onlydo assessments vary between board-certified dermatologists, but the same physician can even make different assessments depending on the time of day of the patient’s evaluation: both inter- and intra-observer variation was shown to be a very high 85 percent. The success and reputation of a clinical trial depends on the data’s reliability and reproducibility, which means consistent evaluations of patient outcomes are a top priority for sponsors.
 
Although physicians use tools like the Psoriasis Area and Severity Index (PASI) and the Eczema Area and Severity Index (EASI) to evaluate patient symptoms, these methods are limited by subjective parameters. The EASI, for example, has the investigator rate redness, thickness, scratching, and lichenification (leatheriness) on a scale of 1 to 3. Despite the investigator’s best intentions, their unique judgement could diverge from those of other investigators in the clinical trial, and produce results that alter the statistical significance of the treatment in question.
 
Fortunately, there are two improved methods to remove subjectivity and improve standardization of visual assessments. The first relies on proper training to minimize human bias, and the second is to provide investigators with assistance in the form of better technology.
 
Standardizing Training Across Investigators
Investigator training, both face-to-face and web-based, is the bedrock for any dermatology clinical study to produce meaningful data and results. The initial training is conducted prior to the trial to establish a baseline and common procedures for all investigators involved in the trial on protocol, measurements, and outcomes. And, training doesn’t stop once a trial is underway. This continued training is under the purview of a medical monitor, whose job is to maintain consistency throughout a clinical trial. A medical monitor may meet with investigators onsite during the course of a clinical trial and provide case studies for evaluation. The monitor provides feedback on the clinical trial procedure and facilitates a discussion that drives outcomes to a common consensus, thereby creating a foundation for more repeatable data as the trial continues.
 
Additionally, medical monitors can use web software to evaluate how investigators are scoring the same patients across different sites, followed up by an onsite visit if necessary to help ensure consistency. Investigators can also use the related online training programs to practice evaluating an indication’s symptoms on their own time.
 
Clinical monitors can track the objectivity of assessments on an ongoing basis to see whether there is divergence between the Investigators Global Assessment (IGA), the FDA’s most trusted endpoint for almost all dermatological study indications, and condition-specific evaluations, such as PASI for psoriasis, or EASI (eczema), and Scoring Atopic Dermatitis (SCORAD). Differences between the scores highlight where there may be problems with the data. To safeguard the reliability of the data, the clinical monitor needs to address these concerns immediately with investigators.
 
Finding Objectivity in Technology
Dermatology clinical trials are adopting new technologies to replace subjectivity with objectivity. Assessing erythema, or level of redness, is a critical aspect of scoring PASI in psoriasis trials. However, the patient’s skin pigment level can complicate this score. A study assessing PASI scoring showed that investigators can use chromometers, which compare color to a reference standard, to objectively measure the lightness, hue, and intensity of skin lesions, regardless of skin type.
 
A JAMA Dermatology study introduced another system of measurement that yielded more objective results than the more established SCORAD index. The Objective Severity Assessment of Atopic Dermatitis (OSAAD) is a composite score of various electronically recorded measurements such as computer-assisted body surface area estimation, skin hydration, and trans-epidermal water loss.
 
Variety may be the spice of life, but variation in data due to subjective assessments could weaken a dermatology clinical trial. Thanks to innovative methods that can improve on the widely accepted scoring indices, or, in some cases, replace them, clinical researchers and sponsors have the means to produce more meaningful clinical trial data, and therefore, more advances in dermatology.
 

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Darcee Duke Strube is Senior Vice President of Novella Clinical’s Dermatology Division. Ms. Strube has more than 35 years of clinical development experience in the dermatology industry with extensive expertise in the therapeutic areas of acne, psoriasis, and rosacea, among others.