When people think of diseases or sicknesses, they usually think of things like the flu, cancer, HIV/AIDS, arthritis, and many others. What people don’t think of, though, are diseases such as Fabry disease, Pompe disease, or mucopolysaccharidosis (MPS). These rare diseases and thousands like them (also called orphan diseases) have incidence rates ranging from 1:200,000 people to 1:1,250,000 and even lower. With such a small patient population, pharmaceutical companies have little incentive to develop drugs for these disorders, and, as such, many patients are forced to go without any form of therapy or are subjected to painful or ineffective treatments. However, one of the most significant moral issues surrounding orphan diseases is the testing process that the drugs go through.
All drugs that are licensed and sold in America undergo a very rigorous trial and review process before they can be brought to market. The Food and Drug Administration (FDA) is the regulatory body in charge of these trials, and the FDA likes thoroughness. They demand that drugs go through several phases of testing, including a toxicity screen on healthy patients, dosage tests, and randomized, double-blind placebo tests in which neither the doctor nor the patient knows if a patient is receiving drug or placebo. In all of these phases, though, one of the most important factors is study population size (the number and diversity of patients tested). In the FDA’s ideal world, the tests would include hundreds of thousands of patients from different areas and diverse backgrounds. In the orphan disease space, though, there are obvious impediments to this that lead to a moral gray area around how new drugs are tested.
With orphan diseases, the entire disease population around the world can be as few as 10,000 patients and possibly even lower. This means that drug trials for rare diseases can have as few as 50 patients in the entire study because there simply isn’t a large enough pool to draw from. The problem that this creates is a lack of certainty in a drug’s effectiveness. A drug or a dosage may erase almost all symptoms in one patient and have almost no effect on another. Perhaps a sub-population with a certain genetic mutation is completely unamenable to the treatment, and that isn’t discovered until years after the product’s release. Problems like these plague the industry and can be hazardous for both the patients and the companies.
Herein lies the problem: is it ethical for the FDA to approve drugs that, if not for their orphan designation, would otherwise fail the FDA’s strict standards? On the one hand, it’s easy to argue that they shouldn’t gain approval. If the companies can’t prove the drugs’ safety and efficacy to the level that the FDA demands, then their product shouldn’t be on the market. On the other hand, these patients need something. The symptoms for many orphan diseases are very serious and destroy the patients’ quality of life. Without those drugs, millions of patients would die and their lives would be hopeless, knowing that no company would ever be able to sufficiently prove safety and efficacy for their drugs. So while I don’t believe that the FDA should recklessly approve any drug with a low patient population, I do believe that each drug needs to be evaluated on a case-by-case basis and that allowances should be made for certain drugs and diseases. This is the current process in place, but it could do with a good deal more clarity and transparency. Drugs are approved or rejected seemingly at random, and the same criteria used to approve one drug are used to reject another. Many pharmaceutical companies don’t even enter the rare disease space at all due to the intimidating nature of dealing with the FDA in orphan disease trials, further inhibiting possible avenues of treatments. We owe these patients better. Pharmaceutical companies should certainly be held to the strictest standards possible, but when it comes to orphan diseases allowances must be made so that these patients can ever have some hope of leading normal lives.