Research on effectiveness of treatment of rare diseases

Charlotte Vrinten Charlotte Vrinten

PhD candidate Charlotte Vrinten examined whether n-of-one trials, which are studies with one single person, are capable of generating proper evidence for the effectiveness of treatment for patients with a rare disease. It is very unusual to perform studies with such low patient numbers. Her research therefore focused considerably on the usability of this type of research for health authorities deciding about market approval and reimbursement of medicines. Charlotte Vrinten completed her PhD  on the 27th of November at Amsterdam UMC.

N-of-one trials are a type of research in which, during multiple cycles, the patient receives two or more treatments; the new treatment (or treatments) as well as the standard treatment (or, in the absence of a standard treatment, a placebo). Similar to large clinical studies, the treatments are preferably given double-blind and in random order. As such, a lot of information is gathered for each patient.

By comparing the results of the new treatment to those of the standard treatment, it is possible to assess whether the new treatment works better for each individual patient. When n-of-one trials are conducted in a similar manner with several patients, it is possible to subsequently assess if the treatment in general is effective for all patients with that condition. In doing so, n-of-one trials can contribute to better care for the individual patient, but also to scientific knowledge on treatment possibilities for patients with a specific rare disease.

Extra important for rare diseases

For rare diseases, there is often a lack of sufficiently large groups of patients available for medical research, which may hinder the search for new treatments. There are approximately 5000 to 8000 rare diseases, and currently there are treatments  available for only 1% of these. Thus, Vrinten’s research offers a valuable contribution to making new treatments available to the approximately 1 million patients in the Netherlands with a rare disease.

PhD research

Charlotte Vrinten conducted two clinical studies: one study in a patient with the rare nerve disease HNPP (hereditary neuropathy with liability to pressure palsies) and one study in four patients with a rare disease of the neuromuscular junction (myasthenia gravis). Both studies showed that the examined treatments were beneficial for the participating patients.

N-of-one trials have barely been used up to now. Therefore, stakeholders were widely involved in the discussion about the usability of the study results for decisions about market approval and reimbursement of treatments. The positive treatment results were presented to the relevant health authorities in the Netherlands, respectively the Medicines Evaluation Board (College ter Beoordeling van Medicijnen) and the National Health Care Institute (Zorginstituut Nederland). Both authorities indicated that they would consider results from this type of research, but afew questions remain with regards to generalizing the treatment outcomes. These questions can be further examined in future research.


Prior to the public defense, a symposium on Personalized Medicine also took place which revolved around the question how innovative medicines can be brought to the market. An important question was how evidence from studies other than large randomized trials can be acceptable for approval and reimbursement.

The dissertation can be downloaded from: