Ethical Considerations in Orphan Drug Approval and Use

Low-quality premarket trials are the accidental side-effects of legislation intended to spur development of orphan drugs.

In 1983, Congress passed the Orphan Drug Act to encourage the discovery of new treatments for rare diseases. The Act led to a boom in the development of orphan drugs, with the FDA approving more than 280 in the last 25 years. Still, it remains an open question whether these drugs are serving the best interests of patients or the industry.

This essay reflects on the ethical outcomes of the Orphan Drug Act and argues that lax FDA oversight has led to the approval of ineffective orphan drugs. 

Key Findings:

  • The FDA routinely waives its most rigorous criteria for orphan drug applications.
  • Years can pass before the FDA conducts follow-up studies to confirm the ineffectiveness of an orphan drug; for the drug midodrine (ProAmatine), more than a decade went by.
  • Patients facing rare diseases may be willing to accept unnecessary risks, lowering their expectations and enabling the FDA to loosen its oversight standards.

This perspective on the outcome of the 1983 Orphan Drug Act, considers the ethical problem now facing clinicians: is it responsible to prescribe an expensive, possibly ineffective orphan drug when the required resources could effectively treat patients with more common diseases?