Background:
Orphan drug regulation was created out of the idea that patients suffering from rare conditions should be entitled to the same quality of treatment as other patients. Some conditions however, are so rare that a thorough clinical development programme, normally required, is practically impossible. In these cases the European Medicines Agency (EMA) can authorise a drug under exceptional circumstances.

Aim and research questions:
This report aims to provide insight into the authorisation under exceptional circumstances of oncology drugs. We tried to answer the following questions: What clinical data were presented by the applicant and what were the considerations by the Committee for Medicinal Products for Human Use (CHMP) for granting exceptional circumstances? What were the additional requirements to be fulfilled by the marketing authorisation holder? What additional data became available on the originally licenced indication, and did it confirm the initial expectations? How do reimbursement agencies assess these drugs? Are there any patient access schemes for these drugs? Do the patients have access to the drugs?

Methods:
This report considered oncology drugs currently licenced under exceptional circumstances. Reimbursement agencies from England, Scotland, Belgium, France and the Netherlands were included. A MEDLINE-search for literature was performed through Pubmed and grey literature was included from EMA and the reimbursement agencies.

Results:
Four oncologic drugs are currently licensed under exceptional circumstances; clofarabine, nelarabine, trabectedin and histamine dihydrochloride. Histamine dihydrochloride was the only drug tested in a phase III trial. For clofarabine, nelarabine and trabectedin the justification for the authorisation under exceptional circumstances was the small size of the patient population. For histamine dihydrochloride it was unclear. Most of the additional requirements by the CHMP considered safety measures and they were not always completed within the set time-frame. The methods of the reimbursement assessments varied. One patient access scheme was identified for trabectedin in England. Some of the drugs were not accessible in some countries and for others it was unclear.

Conclusion and recommendation:
To successfully develop drugs for very rare conditions, it is important that industry, EMA and reimbursement agencies intensify the collaboration. On introduction these drugs cannot always prove their cost-effectiveness, therefore conditional coverage with evidence development, preferably on an international level, should be encouraged and facilitated.