Contributed Commentary by Elisabeth Rowold

July 17, 2018 | A clinical trial’s success relies on unbiased results. Collecting data objectively is a particularly difficult task in dermatology clinical trials, where investigators often assess their patients’ symptoms and treatment outcomes visually. These subjective data lead to variability between dermatologists, and even between observations by the same dermatologist collected at different times on the same day. This variability can impact the ultimate outcome of a clinical trial by obscuring the true effects of an investigational drug.

Several well-known indication-specific diagnostic tests in dermatology yield subjective data. Physicians use the Psoriasis Area and Severity Index (PASI) to assess psoriasis symptoms, the Eczema Area and Severity Index (EASI) to measure the severity, and SCORing Atopic Dermatitis (SCORAD) to evaluate the extent of eczema. None of these measures is fully objective. Common parameters include scaling and thickness, and the PASI includes a measure of “redness” that investigators must assess visually and describe using only their own experience as an external reference. Furthermore, dermatologists don’t have standard methods for measuring the percent of a patient’s skin that is affected by a dermatological condition; rather, they arrive at an estimation for surface area affected by using the size of the patient’s palm, which is thought to represent one percent of body area.

To overcome the challenges associated with subjectivity in dermatology trials, investigators must combine new training practices and imaging techniques that can contribute to the collection of accurate and reproducible, objective measures of dermatological disease.

Training Investigators to Be Objective

Until more objective measures are developed, investigators must be trained and monitored to create as much objectivity as possible. Investigators can, for instance, hold in-person meetings with a medical monitor, wherein they discuss the indication they’re studying and brainstorm ways to measure it more reliably. The medical monitor can show groups of investigators photographs of patients’ lesions and work with them to derive a consensus on how to assess them as consistently as possible.

Investigators can also improve their ability to assess dermatological disease more objectively through webinars and dedicated online training sites. These tools can help investigators become proficient in examining lesions and labeling them consistently. Monitors can collect information on how investigators are scoring lesions across different sites and use these data to support the development of more objective and reproducible data collection methods that regulators will acknowledge as valid.

Furthermore, clinical research associates (CRAs) should watch for how data are collected on the same patient using different measures and watch for inconsistencies. For instance, if an investigator examines a patient with atopic dermatitis and scores the severity of their illness using two different measures, such as the Investigators Global Assessment (IGA) and the EASI, and the two tests yield different results, this may indicate that an investigator is collecting data incorrectly. In cases like this, a CRA must address these concerns with this investigator to ensure that their data is collected in a consistent manner; otherwise, the data cannot be used to support the approval of a drug.

Using Technology to Turn Subjective Measures Objective

Currently, investigators do not have a simple way to measure body surface coverage or to objectively define the color or texture of a lesion. But in the near future, dermatology investigators may be able to scan a patient’s body and measure these parameters objectively using computer assistance.

Investigators commonly use photography to assess dermatological disease, but it is often challenging to use photographs to observe subtle improvements over time. With help from specialized software, however, an investigator can objectively measure changes in disease severity over the course of treatment. This not only reduces variability in the results, but it also could potentially be presented to regulators to demonstrate real improvement in a condition following a drug treatment.  Additionally, in early-stage drug development, the use of chromametry to measure erythema, and the measurement of trans-dermal water loss and skin hydration, are established methods to objectively determine the severity of a skin lesion.

In one 2003 study, researchers developed the Objective Severity Assessment of Atopic Dermatitis (OSAAD) that assesses skin health using electronically-recorded measurements of skin hydration and water loss from the skin, in combination with an objective estimation of body surface area (doi:10.1001/archderm.139.11.1417). They found that OSAAD reliably assessed the severity of atopic dermatitis and that its results significantly correlate with the SCORAD. These researchers believe the OSAAD could serve as a more objective alternative to the SCORAD method.

As these technologies start becoming more prevalent and as they are further developed for broader use in the clinic, dermatology trials are bound to yield more objective and reproducible data. By using objective metrics, investigators can collect data that are less susceptible to inter- and intra-investigator variability. Overall, these metrics will strengthen an investigator’s evidence package and increase the probability that his or her investigational drug will achieve regulatory and commercial success.

Elisabeth Rowold is Director of Project Management in the Dermatology Division (Europe) for Novella Clinical, a Quintiles company. She has more than 23 years of experience in the pharmaceutical industry and more than 14 years of experience in the conduct and oversight of clinical trials spanning all phases of cutaneous safety and efficacy studies. Rowold oversees the Novella Project Management activities in Europe and is responsible for providing strategic leadership, organization, training, and ongoing evaluation and support to the Clinical Operations group. She can be reached at Elisabeth.Rowold@novellaclinical.com.