Summary

Language: English

The development of orphan drugs for the treatment of rare diseases in children under the Regulation EC 1901/2006 is a regulatory challenge, since two problems have to be dealt with at the same time: firstly, the lack of precise data on the mode of action of drugs in children and secondly, the lack of ample insight into and inadequate data on rare diseases. As many as 18 European and national Guidelines have yet to be harmonised. There are still no special methods available for designing, implementing and analysing clinical trials in small populations. However, special approaches aimed at increasing the efficiency of clinical trials are currently being introduced.

The need for statistical efficiency should be weighed against the requirement for clinically relevant and interpretable results.

In situations where obtaining controlled evidence on the clinical efficacy and safety of a new treatment is not possible, regulatories may be asked to accept different approaches, validation and acceptance has to be worked on.

Surrogate endpoints may be acceptable but need to be validated. Their relation to clinical efficacy must be clear so that the balance of risks and benefits can be evaluated.

As regards the unavailability of adequate recruitments for clinical trials, with only few rare disease families available worldwide, detailed pharmacological data and non-clinical pharmacology data of the compound in question may assist the clinical development program.

Patient registers may supply important information on the natural course of the disease and help to assess the effectiveness and safety. In addition, such registers can be used as a source for historical controls. Registers used in this way should contain high quality data. Conditional approval according to Commission Regulation EC No 507/2006 might be necessary in case of smallest sample sizes in the sense of lifelong drug safety observance.

The R&D development of orphan drugs in children facing the dilemma of unavailable data, endless study durations owing to low patient recruitment rates might provide an opportunity for contemplating new study designs and biostatistical methods.

The aim to develop a one-drug-fits-all blockbuster model may be relinquished for more targeted treatment solutions. Creating personalised medicines will be the future of health, and orphan drugs for rare disease populations will teach us how to regulate them. Learning how to develop a regulatory framework for medicinal products being developed in suboptimal conditions for clinical trial conduction valid for as long as these products are on the market will present an even greater challenge.