As early as the mid- to late- 1980s the market started to become increasingly managed (think formularies) and the availability of many inexpensive generic antibiotics even then made it easy to set superiority expectations for new market entries.
About the same time, the widespread use of antibiotics rightfully started to raise concerns with the Infectious Disease community about the development of resistance. Armed with microbiology data and clinical studies, formularies and treatment guidelines were developed to encourage appropriate antibiotic use. Selectively targeted narrow spectrum treatments were preferred to the mindless routine use of broad spectrum agents. To preserve their antimicrobial activity, the use of some uniquely effective agents was further restricted to prior approval by Infectious Disease specialists.
While these were responsible and commendable actions taken, they presented the pharmaceutical industry with a new set of expectations for developing antibiotics. The message was clear. If you want your new antibiotic to be used and you want to be paid a premium price for it, you better have the data (comparative effectiveness) to support that it is better than what we already have (including generic alternatives) and be able to prove it is worth the money (comparative value) you want to charge. And, even if it is that good and costs that much, we are going to make sure it is used selectively in only those patients who absolutely need it.
This wasn’t and still isn’t a very attractive investment opportunity for the industry given the ease of tweaking molecules and the lack of market resistance in other therapeutic categories. Even for companies that decided to have a go at antibiotic drug development, it hasn’t been a very easy road to market. The few products that have gotten approved and done well were able to demonstrate or at least imply a clinical advantage over other drugs.
Now the industry and the FDA are faced with trying to figure out how to design trials that would allow for fair comparisons of different antibiotics. Not satisfied with clinical “non-inferiority” the FDA and the industry seem deadlocked in trial design limbo. More importantly for the industry, the market expectation is for superiority anyway. The company will need near impossible – to – obtain “substantial evidence” in their clinical data to obtain an FDA approved superiority claim needed to promote the antibiotic as superior.
Could other therapeutic categories become similarly unattractive for drug development? When market expectations and regulatory hurdles become impractical and seemingly financially infeasible pharmaceutical companies will make one of two choices. They will take on the task in hopes of beating the challenging circumstances so they can charge a super premium price when they bring that superior product to market. Or, more likely, they will gravitate to therapeutic categories with lower market expectations and fewer regulatory hurdles.
Many pharmaceutical companies will fail making the first choice and many diseases will never have optimal treatments given the second choice.