DISCUSSION: Traditional clinical trial designs, validation, and evaluation methodologies used for nonorphan drugs often prove unsuitable for orphan drugs, given the small patient populations, sometimes fewer than 1000 cases. There is an increasing need for accessible therapies and both regulators as well as industry are trying to develop affordable and effective drugs to address this need. Despite several steps that have been taken, the timely development of drugs remains a challenge. One of the reasons behind the long development timeline is the recruitment, retention, and conduct of rare disease trials. To optimize the development timelines of orphan drugs in the EU, it is important to ensure that the safety and efficacy of the product is not compromised. Industry and regulatory agencies must implement innovative trial designs, devise flexible policies, and incorporate real-world data for assessing clinical outcomes.
CONCLUSION: Collaboration among academic institutions, pharmaceutical companies (both small and major), patient groups, and health authorities is crucial in overcoming obstacles related to clinical trials and providing assistance and creative ideas. The ultimate objective of granting rare disease patients timely and affordable access to medications with a positive balance between benefits and risks is to be met.
Methods: Relevant peer-reviewed articles were identified by means of a systematic review. The literature was searched from 20 May 2020 to 20 June 2020. The search included the databases PubMed, Scopus and Web of Science (2010 - April 2020). A total of 4,139 papers related to rare diseases were identified; with 1,205 papers obtained from Scopus; 2,476 papers from PubMed; and 458 from Web of Science with keyword search "ethics" AND "rare" AND "disease", "ethical" AND "orphan", "ethical" AND "orphan" AND "drug", and "ethical" AND "rare" AND "disease". Finally, XX studies were chosen for further analysis.
Results: The main findings reveal five main ethical issues. The most essential one shows that funding research and development in the field of orphan drugs poses an almost impossible dilemma. Other issues include the significance of non-economic values like compassion and beneficence in decision-making related to orphan drugs and rare diseases; the identification of limits to labelling diseases as rare; barriers to global, supranational and international cooperation; and last but not least, determining and establishing panels of decision-makers.
Conclusions: A strictly global approach would be the most appropriate way to deal with rare diseases. Nonetheless, international, let alone global, cooperation seems to be completely beyond the reach of the current international community, although the EU, for instance, has a centralized procedure for labelling orphan drugs. This deficit in international cooperation can be partly explained by the fact that the current technologically globalized world still lacks globally accepted ethical values and rules. This is further aggravated by unresolved international and intercultural conflicts. In addition, the sub-interests of various parties as well as the lack of desire to deal with other people's problems need to be taken into account. The aforementioned problems are difficult to avoid. Nevertheless, let us be cautiously optimistic. At least, there are people who raise ethical questions about rare diseases and orphan drugs.
METHODS: The study consists of literature reviews and key stakeholders interviews in six focus countries, including the Philippines, Singapore, Malaysia, Indonesia, Vietnam, and Thailand and five countries as best practice, comprising of France, Canada, Australia, Taiwan, and South Korea. Rare disease management initiatives across each country were examined based on the World Health Organization's framework for action in strengthening health systems.
RESULTS: The results suggest rare disease management remains challenging across Southeast Asia, as many of the focus countries face fundamental issues from basic healthcare systems to funding. Nonetheless, there are substantial improvement opportunities, including leveraging best practices from around the world and organising a multi-stakeholder and regional approach and strategy.
CONCLUSIONS: Southeast Asian countries have made significant progress in the management of rare disease, but there remain key areas for substantial development opportunities.