Ann Arbor, Mich. — Accurate, reliable, and appropriate documentation of the severity of psoriasis is important in clinical practice and essential for clinical trial research, says Charles N. Ellis, M.D.
Ann Arbor, Mich. - Accurate, reliable, and appropriate documentation of the severity of psoriasis is important in clinical practice and essential for clinical trial research, says Charles N. Ellis, M.D.
"In clinical trials in particular, quantification of the disease is critical to measure the efficacy of an investigational treatment by comparing the severity of disease before therapy to that measured after treatment," says Dr. Ellis, professor and associate chair, department of dermatology, University of Michigan Medical School.
Dr. Ellis describes the Lattice System Physician's Global Assessment (LS-PGA), which he designed in an effort to create a standard system for rating psoriasis that overcomes both the difficulty of interpreting data from a wide variety of systems as well as the specific problems associated with the two commonly used scoring systems - the Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA).
"We define response to treatment as the difference between baseline and post-treatment," Dr. Ellis says, adding that the assessment is not at all straightforward, largely because of the range and differing importance of the variables to be considered.
These include the percent of the body surface area (BSA) that is involved and the quality of the lesions that must be examined and evaluated for the degree of elevation and erythema and the amount of scale.
Dr. Ellis says that in developing the LS-PGA he took into account the needs of regulators at the FDA and the European equivalent, the European Medicines Agency (EMEA), and he considered the desires of clinical researchers who actually perform the studies submitted to the regulatory agencies.
"We know that research investigators need a reproducible assessment method with clear definitions that is quick and easy to perform, while regulators seek 'static' ratings indicating severity at the time the patient is seen, with segmented results reflecting clinical relevance to patients," he says.
Problems with PASI, PGA
With PASI, plaque qualities (e.g., induration) are not defined, and confusion is created by the use of different terms in different studies. The final result ranges from 0 to 72 - numbers that have no intrinsic meaning, Dr. Ellis says. What's more, erythema, infiltration and desquamation are all weighted equally in the PASI calculation, which is quite complex. Plaque elevation is widely considered more important than the other two plaque qualities.
In the case of the PGA, explains Dr. Ellis, the methods are usually not defined at all, and when definitions are present, they often differ from one study to the next.
Keeping in mind the shortcomings of these systems, as well as the needs of researchers and regulators, Dr. Ellis specifically designed the LS-PGA with clear definitions and weighting of the different variables.
"With our step-by-step Lattice system, plaque qualities are defined and averaged over the entire body, and plaque elevation is weighted preferentially. Involvement of the body surface is broken into easily estimated ranges. The final eight-step score ranges from Clear to Very Severe - terms with intrinsic and intuitive meanings," Dr. Ellis says.
He notes that the investigator checks four boxes, and the final assessment is calculated by computer.
"The Lattice system has undergone two validations studies, one in the U.S. and one in England, and has been used in a number of trials, including one multinational trial of over 2,500 patients," adds Dr. Ellis, who says he designed another version for use in doctors' offices to prove the need for a patient to receive systemic therapy and to track patient responses.
Dr. Ellis emphasizes that quantifying overall burden of disease may be more complex than just the calculating of the objective measure of severity provided by rating systems such as the LS-PGA.