Study Phases: For Developing a Drug
Now that the United States Food and Drug Administration (FDA) has approved Lyrica (pregabalin), Cymbalta (duloxetine), and Savella (milnacipran) for the treatment of fibromyalgia, many pharmaceutical companies are encouraged by this progress. As more companies begin to test their medications for relieving the symptoms of fibromyalgia, you may be wondering: How long does it take for the FDA to approve a drug, and how many patients need to be tested for a particular medical condition?
After a potential medication is developed in the laboratory, it must be tested in lab animals (typically rats or mice) to show that it does not produce any evidence of harmful or toxic effects. The FDA has specific requirements that must be met during the lab animal tests before a drug can be tried in human subjects. This development animal research stage can take any number of years and is expensive because only a small percentage of agents developed can be proven by FDA standards to be safe enough for testing in humans.
Treatment studies in humans, often referred to as clinical trials, is a process that often takes about seven years and requires that the new agent be evaluated in 1,200 to 3,000 patients. If the drug is already on the market in the United States, it can be fast-tracked through the FDA for a new indicated use in two to three years, which was the case for Lyrica. Even if a drug is already available in Europe with a good safety record, it must undergo lab animal and clinical trial testing to become FDA-approved for use in the United States. Although a large number of patients are tested, it often represents just a tiny percentage of people with a given medical condition. This is especially the case with fibromyalgia, in which 3-5% of the general population has this condition.
For a drug to be FDA-approved for the specific treatment of fibromyalgia (even if it is already on the market for another condition), the process begins with a Phase I trial involving 20-80 patients to evaluate safety, effective dose ranges, and identify side effects. This trial is typically initiated by one investigator at one treatment center. Assuming the results are favorable, a Phase II trial involving about 200 patients is performed with the same goals in mind as the Phase I trial. However, this second study usually involves multiple treatment centers across the United States to include a more diverse population of patients that can be studied by more than one investigator. Ideally, the Phase II trial is successful and it identifies the most effective dose with the least amount of side effects.
When the FDA gives a drug company the go-ahead to begin Phase III trials, this is a very promising sign that the drug might be approved for the condition or patient population being tested. Roughly 1,000 to 3,000 patients are evaluated in Phase III trials to confirm the drug’s effectiveness, safety profile, and common side effects. Often 50-100 treatment centers are involved. This FDA phase may consist of a short-term, placebo-controlled trial (two to three months) followed by a six- to 12-month trial to determine if the drug maintains its effectiveness in the long-term.
Favorable data from the Phase III trials could result in the FDA’s permission to release the drug onto the prescription market or approve it for a new indicated use. After a medication is FDA-approved, the drug company must perform Phase IV trials to provide additional information to prescribing physicians and the studies involved are sometimes referred to as the post-marketing trials. If the drug is new (i.e., it has not already been FDA-approved for another indicated use), some physicians may wait until the Phase IV trial results are published before they feel confident enough to prescribe the drug to a large number of their patients. In the end, only one out of every 27 drugs ever get FDA approved for prescription sale.
If a drug is already FDA-approved for a condition other than fibromyalgia, your physician may chose to prescribe it to for you as off-label treatment medication. Off-label means that a drug is prescribed for a condition or medical situation that it was not specifically FDA-approved for. It is simply not feasible for drug companies to get their medications FDA-approved for all possible conditions, but physicians must adhere to professional standards by prescribing off-label drugs in a logical and medically accepted fashion. Say, for example, a drug is already FDA-approved for treating muscle pain associated with diabetes with very few side effects. It’s reasonable to assume that many physicians would prescribe this drug off-label to treat muscle pain in their fibromyalgia patients. Similarly, Ambien and Lunesta are both approved for treating insomnia and many fibromyalgia patients are prescribed these two medications off-label to reduce their difficulties sleeping at night.
Having a drug FDA-approved for fibromyalgia does not automatically mean that one’s health insurance will cover the drug or that the co-pay will be smaller. The FDA has no jurisdiction over the insurance industry. However, when a drug is prescribed off-label, there is a higher likelihood that an insurance company will deny coverage.
Despite the initial battles that patients may face with the insurance industry, there are many benefits of having medications FDA-approved for fibromyalgia:
- greater treatment options,
- improved public awareness and acceptance of fibromyalgia as a credible condition that requires medical treatment, and most importantly,
- aggressive physician education programs on fibromyalgia sponsored by the pharmaceutical industry so that it will be easier to find a knowledgeable doctor who really cares!