I first became interested in this question after the ADA Scientific Sessions in Boston. There I listened to a presentation of Joseph A. DiMasi, PhD, who analyzes the economics of health care at the Tufts University Center for the Study of Drug Development. Although not an expert in diabetes care himself, he was able to find in his research that the approval pipeline for diabetes treatment is indeed slow.
“We’ve seen very large trials and lengthening clinical development times, which would suggest larger than average development costs,” DiMasi said.
The FDA is a jack-of-all-trades regulatory agency. It receives requests for regulatory approval in areas way beyond food, drugs and equipment. In recent years, marketing and formulation of tobacco products and additives and smokeless products have fallen within its reach. Veterinary practices and medications have a bearing upon medical research, and so are subject to FDA regulation, as are prosthetics, motorized wheelchairs, and surgical and radiological devices. The agency even regulates components of materials used to package food, personal care products, pet food, and surgical instruments.
The agency started out in the Theodore Roosevelt Administration, when slaughterhouses and packing plants were as dangerous to human health as modern Superfund sites, and snake oil salesmen roamed the western frontier with cures for vapors, rheumatism, and “female hysteria.” The federal Pure Food and Drug Act of 1906 incorporated safeguards previously handled, evidently not very well, by the Agriculture Department.
In years following, the act was amended to broaden the agency’s regulatory scope to include the regulation of food, drug, and cosmetic manufacturing practices. By 1984, drug price competition and restoration of patent protections had come within the FDA’s purview. The law underwent significant and substantial changes again in 1992, with amendments requiring that any proposed therapeutic innovation show it works and improves on existing therapies.
Here’s the FDA’s modern medical workload: 20 to 30 new drugs a year (new molecular formulations — this does not include the thousands of changes to existing cleared drugs it must review) and 50 to 70 new devices — not counting about 4,000 improvements to devices and submissions of post-market quality assurance reports. To meet this demand, priorities have to be set, so the FDA follows a four-tier system of assigning its resources and putting applications on expedited timetables, based upon the needs of the country’s health care delivery system.
The highest priority (fast-track) cases are proposals that can lead to improvements in diagnosis, overcome dangerous side effects of existing therapies, or meet an emerging public health crisis. A 60-day deadline is imposed upon the agency to determine whether the application stays on the fast track to approval or is assigned a different priority. The FDA assigns senior staff to these projects, and its staff and manufacturers’ representatives work collaboratively.
Next in the hierarchy are breakthrough therapies, which indicate therapies that possibly provide a clear advantage over available therapies. Again, the agency is obliged to take action also within 60 days of initial filing to determine whether to continue pursuit of breakthrough status or reassign to a different level of priority. Progress reports are submitted by the applicant on a more frequent schedule than for other review categories, and the FDA and applicants staff hold regular meetings to confer on trial data.
Accelerated status is granted primarily to laboratory devices or measurement equipment where it appears evident that reliability can be established over a relatively short period of time versus a year or more of experimental use. In the case of a drug application, accelerated status is granted to drugs that can extend the survival time of patients and/or shows improved short-term success in attacking a disease.
In considering which of the three categories above is most appropriate for the handling of a pre-market investigation, the agency takes into account evidence of past failures of similar drugs or devices, and the number of patients who potentially could benefit. It’s important to remember that it’s not the agency’s job to secure new competitive opportunities for pharmaceutical companies. The agency is charged with making sure that therapies are first safe, and then effective. A tweaking of a component of a biosimilar insulin which might benefit a small cross-section of patients only from the standpoint of convenience will not climb to the top of the inbox.
The fourth expedited review category is called priority review. Here, a drug or device is very often an alteration to that which has already received final clearance or is making its way along successfully in another expedited review category. An example would be the approval that (the now closed pump maker) Asante received last year to make modest mechanical changes in its disposable Pearl pump assembly, which would have no adverse effect upon durability or service life of the Pearl, or of the Snap version of the pump, which was proceeding to market.
A survey of pre-market approval filings over the past half dozen years reveals that the vast majority of diabetes drug and device applicants are granted priority handling, and proceed from pre-market notification to clearance in a year or less.
It’s possible that diabetes treatment is a victim of its own success. Because people with diabetes can have long lifespans and existing treatments can, in theory, control blood sugar levels relatively well, the FDA doesn’t give new treatments or improvements higher priority. Likewise, established drug companies may have less financial incentive to risk financial resources for true breakthroughs in diabetes treatments. If this is ever to change, it might require political pressure, either to prod legislators to change FDA criteria or to educate regulators about the limitations of current treatment options.
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