Contact Lenses are regulated by the Food and Drug Administration (F.D.A.) as Class 3 Medical Devices. Class 3 medical devices are defined by the FDA as those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury.
Class 3 medical devices require the highest level of evidence for Premarket approval (PMA), which is a process to evaluate safety and effectiveness before the product can be brought to market . Clinical studies, scientific documentation, and reviews are required. There can also be post marketing surveillance studies after a new contact lens is released to look for further problems. Prescription drugs require a similar but much more involved process before they reach the market place.
A press release from the National Eye Institute in 2008 stated a phase1 gene therapy clinical trial showed promising results for a blinding disease known as a congenital form (present at birth) of Lebers Optic Atrophy. The retinal pigment epithelium is the layer of the tissue lining the back of the eye, the retina, that nourishes the rod and cone cells we see with. A mutation in a retinal pigment epithelium gene causes these cells to respond very poorly to light and results in loss of vision. Frequently we see news on gene therapy and are led to believe everything will be cured by in short order. Patients in the study received a sub-retinal injection to replace the defective gene in areas of the retina that were still relatively healthy. Each patient had visual impairment that had been present since birth due to the defective gene. Over a 90-day period there was significant improvement in vision. Day vision was improved by 50-fold and night vision by 63,000-fold compared to pre-treatment levels. Restored vision was localized to the area of treatment in the treated eye.
We tend to think of new drugs and medical devices as overnight miracles but researchers have been working for 15 years to get to this point. The new generation of 30 day wear contact lenses actually started with research done in the 1970’s. All new prescription drugs and medical devices face the funding and regulatory structures that are required to pass the requirements for approval. While this process is frustrating and fraught with problems, if you spend a little time reading about the equivalent processes and equivalent oversight agency in China, you will gain a greater appreciation for the system we do have in place.
Clinical trials for prescription drugs proceed in four phases over a period of years and millions of dollars. Actually there is a new phase zero but since it is still in transition we will cover only the 4 main phases.
The first testing of drugs in humans as referred to as phase 1. Typically this involves healthy individuals in a group less than 50. The main goal of phase one trials are the to make sure there are no glaring safety issues and gain some understanding of how the drug works and is processed in the body. Normally, a small (20-50) group of healthy volunteers will be selected.
Phase 2 trials are mostly just an extension of phase 1 with several hundred patients. They also pry a litle more into the amount of drugs needed to be effective in treatment and what time intervals are needed to administer the medication..
Phase 3 studies are what brings a new drug to the corner pharmacy. Phase 3 trials may base tentative approval on only several hundred patients, and typically no more than 2000-3000 are in this phase. For you, that does mean a 1 in 10,000 lethal effect may not be known initially, or some other surprises may not be uncovered for several years. In Phase 3 patients are split into groups with one group receiving placebos (no active medication) and another group receives the actual medication, Researchers typically don’t know who is getting what until the end of the study. Occasionally, it becomes so evident that a drug is saving lives or vision that the study is stopped as it is not ethical to deprive the patients receiving placebos of the full benefits of the new drug. The Women’s Health Initiative study on hormone replacement therapy for menopause was an example of this. The study was terminated early when it was determined that hormone therapy increased the risk of breast cancer.
Phase 4 is where the good, the bad, and the ugly comes out. This is also called the Post Marketing Surveillance Phase. Phase 4 trials involve the long term safety monitoring where the 1 in a million problems start to be seen over time. Also the interactions with other medications may become more evident, and idiosyncrtic reactions (really strange ones specific to an individual) may appear. Long term effects (Remeber Phen-Fen the diet drug that caused heart problems) may show up after a number of years.
Our Fort Collins office has taken part in several optometrist clinical studies with contact lenses as some of you know and participated in. These are somewhat like the phase 3 clinical trials for medications. A lens may be studied by eye doctors on 500-600 patients prior to approval. While there is no such thing as a placebo lens, a contact lenses that has been approved in the past can be used on one eye as a comparison control. It a lot of fun to be involved in these emerging contact lens products but also a lot of record keeping, and when patients don’t keep their appointments the stipulations are pretty rigid about dropping them from the study. Generally we do not expect the same type of serious complications with contact lenses that can be seen with new medications.
One final bit of information. Sometimes things works out in odd ways. While drugs may have undergone all 4 phases and have approval for specific conditions, that does not restrict doctors from using medications “off label” in ways they have not been studied and approved for.The Food and Drug Administration regulates drugs and medical devices, not Doctors. Currently, the standard of care for certain eye infections is “off label eye drops.” It would be considered substandard care to use the FDA approved medication in these special cases. This a very uncommon occurrence indicative of some weak point in the system where clinical experience is ahead of the curve. Someday there will be a way to account for these situations. Until then, we will continue to do the best with what we know today.