Conducting high-quality randomized clinical trials (RCTs) in rare diseases such as myasthenia gravis (MG) can be challenging. Researchers at Duke University and Harvard Medical School reviewed study design options that could enhance the assessment of potential new therapies for MG.
The study, “Comparative effectiveness clinical trials to advance treatment of myasthenia gravis,” was published in the Annals of the New York Academy of Sciences.
The broad spectrum of features and symptoms of this disease, including the prolonged time to response for many immunosuppressive drugs, makes it hard to fulfill the generally strict enrollment criteria of RCTs.
In addition, traveling and treatment logistics associated with this type of study can also contribute to their lack of accuracy and failure.
“Additional methods of generating high-quality evidence to inform clinical decision making and payer coverage need to be considered,” the researchers stated. “Because of the difficulty designing and implementing large RCTs in MG, prospective, observational cohort studies of comparative effectiveness of treatments for MG are an attractive alternative study design.”
The researchers believe that observational studies may provide valuable effectiveness data on treatments for MG. They are based on the evaluation of the beneficial effects of new therapies in a real-world clinical setting. This approach eases the generalization of the finding to the clinic, but they can also be less resource-intensive and costly than randomized clinical trials.
Pragmatic clinical trials (PCTs) can also measure treatment effectiveness in real-world clinical practice. This type of study has an intermediate design between RCTs and observational studies.
PCTs aim to determine the effectiveness of new therapies in real-life clinical settings, but study participants are still randomized and the outcome readout is blinded. This structure reduces the bias inherent in observational studies and it can improve the chances of enrollment success compared to RCTs without compromising the validity of the data.
The publication of international consensus guidance for myasthenia gravis treatment, as well as the development of MG standardized databases with common data elements, have improved the feasibility of observational effectiveness studies.
The researchers said the Myasthenia Gravis Foundation of America (MGFA) is establishing a “network of clinics specializing in the treatment of MG (the MGFA Clinical Care Network).”
Such a strategy would allow clinical information to be kept in a standard format, which will in turn support the development of comparative effectiveness studies.
“A multicenter CER [comparative effectiveness research] study in MG patients that has been funded by the PCORI is expected to yield important insights into real-world outcomes with the most commonly used [immunosuppressive] medications,” the researchers wrote.