Individual Treatment Trials—Do Experts Know and Use This Option to Improve the Treatability of Mucopolysaccharidosis?

Abstract

Mucopolysaccharidoses (MPS) are a group of rare, heterogeneous, lysosomal storage disorders. Patients show a broad spectrum of clinical features with a substantial unmet medical need. Individual treatment trials (ITTs) might be a valid, time- and cost-efficient way to facilitate personalized medicine in the sense of drug repurposing in MPS. However, this treatment option has so far hardly been used—at least hardly been reported or published. Therefore, we aimed to investigate the awareness and utilization of ITTs among MPS clinicians, as well as the potential challenges and innovative approaches to overcome key hurdles, by using an international expert survey on ITTs, namely, ESITT. Although 74% (20/27) were familiar with the concept of ITTs, only 37% (10/27) ever used it, and subsequently only 15% (2/16) published their results. The indicated hurdles of ITTs in MPS were mainly the lack of time and know-how. An evidence-based tool, which provides resources and expertise needed for high-quality ITTs, was highly appreciated by the vast majority (89%; 23/26). The ESITT highlights a serious deficiency of ITT implementation in MPS—a promising option to improve its treatability. Furthermore, we discuss the challenges and innovative approaches to overcome key barriers to ITTs in MPS.

RETRACTED: An Innovative Tool for Evidence-Based, Personalized Treatment Trials in Mucopolysaccharidosis

“…As many immunomodulatory drugs are market-approved for other indications, ITTs combined with these are an obvious and time-efficient option to improve the treatability of MPS [ 20 , 21 ]. Drug repurposing is an EMA-recommended [ 27 ], highly personalizable [ 68 ] option to improve treatability in rare disorders [ 11 , 12 , 13 ], which is still underutilized, and only a few MPS centers make use of this, as shown by us previously [ 22 ].…”

“…Key hurdles, expressed by experts in our survey, included time and other efforts needed to plan and conduct the trials, as well as a lack of training in ITTs [ 22 ]. This is in line with other work that has shown that the know-how and efforts associated with profound RBAs needed to justify and plan ITTs are also key barriers in other fields [ 69 ].…”

“…The main obstacles were a lack of know-how and resources for systematic risk–benefit assessments (RBAs) of the experimental therapy and for the design and conduct of ITTs. A putative tool that facilitates systematic evidence-based RBAs was expected to overcome these barriers by the majority of MPS experts [ 22 ].…”

Development of Medicines for Rare Pediatric Diseases

“…ITTs rely on the use of a treatment without scientifically proven efficacy or outside indications when established treatment methods are no longer helpful. Therefore, ITTs can be extremely useful for investigating new effects of care in diseases with unsatisfactory therapies [12].…”