Dr. Joel Gelfand discusses the value in performing pragmatic research to generate real-world data for better dermatology patient outcomes.
Joel M. Gelfand, MD, MSCE, Professor of Dermatology and Epidemiology, University of Pennsylvania, Perelman School of Medicine
“I spoke about a topic called pragmatic clinical trials. And this is a new area of research in the field of dermatology although it has been around for decades in the broader field of medicine,” said Joel M. Gelfand, MD, MSCE, who presented “Pragmatic Clinical Trials” at this year’s Masterclasses in Dermatology.
“This is a critical area that [we] in dermatology, particularly in the U.S., need to get more familiar with if we want to advance our specialty.”
A pragmatic trial differs from a traditional clinical trial in that it takes a real-world approach, according to Dr. Gelfand.
“…it’s designed to reflect how we actually practice medicine, and it answers the question, ‘How well does this therapy or this intervention work under real-world clinical practice conditions?’”
By comparison, clinical trials seek efficacy and safety data for FDA drug approvals, he said.
“Usually, they have 30 or 40 inclusion-exclusion criteria before patients are allowed into the study. And so what we know is that the data that we use to get drugs approved often doesn’t reflect patients that we treat in the real world.”
Real world studies conducted in Europe have shown that approximately one-third of psoriasis patients on systemic agents would not have been candidates for those clinical trials1; other studies have shown that patients who don’t meet inclusion criteria experience less efficacy and more risk for serious adverse events,2said Dr. Gelfand.
“And this is not unique to dermatology [or] unique to psoriasis. It’s true across many fields of medicine. And for this reason, increasingly stakeholders, like patients and payers, want to know how therapies work under real world conditions. And also, more importantly, as we have more treatment options, we want to know how things work—one strategy compared to another strategy in the real-world treatment conditions.”
One such study, the Light Treatment Effectiveness Study (LITE Study), 3,4 is a pragmatic study that compares the effectiveness of using at home vs. in-office phototherapy to treat psoriasis. The study has more than 770 people enrolled at 42 sites in the U.S., said Dr. Gelfand.
“The inclusion criteria are, basically, you’re 12 or older, you have plaque or guttate psoriasis, the dermatologist feels it’s medically appropriate for the patient to be treated at home or in the office, and the patient agrees. That’s it.”
According to Dr. Gelfand, there are no therapy washouts and some of the people enrolled would never be allowed in standard clinical trials, for example, pregnant women on biologics.
“The idea would be that this type of study will generate the kind of real-world data needed to help patients, providers, and payers make better decisions around use of phototherapy for plaque or guttate psoriasis.”
The study has shown patients expect to pay an average of $750 in copays and spend 36 hours of travel time for a 12-week course of in-office treatment, said Dr. Gelfand.
“That’s the kind of data we’re generating in large numbers of people that hopefully will help payers look at this and say, hmm, you know, this is very burdensome what we’re doing to patients if we insist they use phototherapy before they can go on a biologic, or if we’re not willing to make home phototherapy available for them….”
This study is also looking to provide patient-centered data that answers the question, “Given my individual patient characteristics and my preferences, what’s my best treatment option?” he said.
“And so, in this particular trial, we could wonder well, maybe phototherapy will work differently based on what your skin type is… so we’ll be answering this question to show that the treatment at home versus office works just as well whether you’re darker complected or medium complected or [have] fairly complected skin.”
Another pragmatic trial that’s being planned looks at a new way of controlling cardiovascular risk factors in people with psoriasis using the standard of care guidelines from the American Academy of Dermatology and National Psoriasis Foundation,5 said Dr. Gelfand.
“Based on the 2018 American College of Cardiology and American Heart Association guidelines, psoriasis is defined as a cardiovascular risk enhancer, warranting more intensive management of CV risk factors.”
“Many primary care doctors aren’t aware of this, so they just use the regular guidelines not realizing that if you have a cardiovascular risk enhancer like psoriasis or inflammatory arthritis or metabolic syndrome, and many of our patients by definition have one of those (often all three). They should be using statins earlier in the course of their risk of heart disease, usually at a 5% or higher risk of heart disease over the next 10 years.”
Early findings from a pilot study were presented at the International Societies for Investigative Dermatology meeting in Tokyo in May,2 he said.
“…in 85 patients we screened at four sites across the country, almost all (about 90%) went through the process of getting their risk factors checked—doing their blood pressure at home, getting their cholesterol done, and meeting with a care coordinator. And what this tells you is that patients are highly motivated. When the doctor tells them, ‘Oh, you have a higher risk related to psoriasis,’ they will follow through when a workup needs to be done.”
Another finding: about 25% of patients needed medical intervention to reduce their cardiovascular risk, said Dr. Gelfand.
“We’re finding that when patient follow through on recommendations, their cholesterol went down dramatically and their risk went down dramatically. One patient was diagnosed with triple vessel disease, meaning he was very high risk of having a cardiovascular event. These are people who, had they not been involved in this work with us, this pragmatic study, would have been at high risk of having an event that could have been easily prevented just by following standard of care.”
Inclusion criteria for the trial are simply presenting in the office for management of psoriasis, being between the ages of 40 to 75, not currently on cholesterol lowering medications, and with no known cardiovascular disease.
“Basically, we’re targeting patients with psoriasis for primary prevention, per guidelines. And they’re just being seen in routine care and follow up just like the LITE patients are all being recruited from routine clinical practice.”
“This is an example of doing pragmatic research, and hopefully we can change the standard of care that will lead to better outcomes for our patients.”
References:
- Mason KJ, Barker JNWN, Smith CH, et al. Comparison of Drug Discontinuation, Effectiveness, and Safety Between Clinical Trial Eligible and Ineligible Patients in BADBIR. JAMA Dermatol. 2018 May 1;154(5):581-588. doi: 10.1001/jamadermatol.2018.0183. Erratum in: JAMA Dermatol. 2018 Jul 1;154(7):852. PMID: 29590279; PMCID: PMC5876819.
- Garcia-Doval I, Carretero G, Vanaclocha F, et al. Risk of serious adverse events associated with biologic and nonbiologic psoriasis systemic therapy: patients ineligible vs eligible for randomized controlled trials. Arch Dermatol. 2012 Apr;148(4):463-70. doi: 10.1001/archdermatol.2011.2768. PMID: 22508869.
- The LITE Study: Light Treatment Effectiveness Study. Available at https://www.thelitestudy.com. Accessed: May 16, 2023
- Gelfand JM, Wan J, Callis Duffin K, et al. Comparative effectiveness of commonly used systemic treatments or phototherapy for moderate to severe plaque psoriasis in the clinical practice setting. Arch Dermatol. 2012 Apr;148(4):487-94. doi: 10.1001/archdermatol.2012.370. PMID: 22508874; PMCID: PMC3476943.
- Neopaney A, Wang S, Shin DB, Fitzsimmons RC, Baez SV, Armstrong AW, Barbieri JS, Beidas RS, Garshick MS, Mehta NN, Ogdie AR, Gelfand JM Prevention of Cardiovascular Disease and Mortality in Patients With Psoriasis or Psoriatic Arthritis (CP3) Study: Preliminary Results Presented at the International Society for Investigative Dermatology Tokyo Japan May 13, 2023.