Newer drug delivery methods a disruptive change for physicians, patients and industry
A great deal of human and financial capital is being invested to develop alternatives to eye drops for treating many ocular diseases. We ophthalmologists have relied on drops to treat most every nonsurgical ocular problem for centuries. Why the sudden and growing interest in alternatives to drops? After all, we have very strong evidence that drops are safe and effective when used to treat many ocular problems. I believe there are several factors driving the energetic search for so-called “dropless” and “extended-release” ocular pharmacologic agent delivery methods. In this effort, we are not developing new innovative molecules, just new innovative delivery methods.
The first driving force is the irrefutable fact that patients just do not take their drops as prescribed. Some cannot because of physical or mental disability, but most simply choose not to follow the recommended method of drop delivery and dosage regimen. Compliance with a prescribed drop in chronic therapy falls below 50% within 6 months and as low as 15% by 4 years in one recent study on glaucoma treatment. In addition, when multiple drops are prescribed, compliance falls even further. Finally, even when patients are highly motivated, many do not take their drops properly.
Ophthalmologists bear some responsibility here, as we do not always properly instruct patients on proper drop application. And it is the rare ophthalmologist who asks their patients to demonstrate their drop application technique in front of them. The worst example I have seen in my career is the patient who opened her mouth and placed the drop on her tongue when demonstrating to me how she applied her glaucoma medication. No wonder her pressures were poorly controlled despite her insistence that she took her drops every day. Still, studies show that despite repeated intense written and verbal instructions, patients just do not take their drops properly. Those suspensions that need to be shaken are not shaken. The intervals between successive drop placement are inadequate. Eyes are not closed after application, and nasolacrimal finger pressure is not applied. And of course, there are patients with severe arthritis, lack of functioning limbs and dementia who cannot be expected to comply with a drop regimen without help, and help is often lacking or expensive.
Second, drops have become very expensive. As patients have become ever more responsible for sharing in the cost of their care, they are amazed and distressed by the cost of their drops. So much so in some cases that they simply refuse to buy them. The pricing of pharmaceuticals is a complex topic, with many hands in the till before the patient receives the prescription, but it is an everyday fact for the practicing ophthalmologist that patients are not happy with the cost of their drops and are pushing for an alternative. Unfortunately, it is usually the doctor in the trenches, who has little control, who bears the brunt of this growing patient dissatisfaction.
Lack of compliance in drop delivery is a major unmet need that must be addressed because noncompliance in many cases can lead to severe postoperative complications, vision loss and even blindness. To overcome the major unmet need of poor patient compliance, innovation is required. These innovations will, in my opinion, be disruptive to both the practicing ophthalmologist and the industry that supports us, but any doctor or pharmaceutical company that ignores the patient-driven desire for dropless extended-release therapy will do so at their own peril.
The cover story in this issue discusses some of the efforts currently funded, and there are many more not mentioned. The new treatment delivery models will, in well-conducted clinical trials, need to be proven safe and effective. Each disease will have a different treatment profile that will be ideal. For example, the treatment of inflammation after cataract surgery might call for an extended-release steroid therapy that extends for 4 to 6 weeks and tapers in dose over time, while for glaucoma the preference would be a sustained dose of drug for 3 or more months. In retinal disease, some specialists I have talked with want a 2- to 3-month sustained-release anti-VEGF, while others want something that lasts 4 to 6 months or even longer. In the end, it will be ideal to have multiple choices and, as always, customize the treatment to the patient’s needs.
Finally, while the overall development costs will be high, in the end the extended-release drug delivery model that is most successful will work as well as or better than drops, enhance patient outcomes by eliminating compliance issues, increase doctor control and confidence, generate high patient satisfaction in regards to cosmesis, convenience and comfort, and actually cost the system less than the current drop alternative. The cost savings can come in the form of reduced direct cost, reduced patient visit cost, reduced complications from better postoperative infection and inflammation prophylaxis, or a reduced cost to society when diseases such as glaucoma do not progress to blindness. Successful product developers would be wise to consider overall cost and the socioeconomic benefit of their proposed therapy in their development plans from day 1. In addition, if additional work is required by the ophthalmologist to apply the extended-release device, fair reimbursement to the provider would be a necessity for broad adoption.
We have our first extended-release drug delivery devices approved by the FDA in the U.S., and we can expect many more over the next decade. Time will tell, but I see this as a disruptive change that will continue to gain momentum in how we treat eye disease as we slowly but continuously trend away from a centuries old reliance on eye drops.