When studying a new drug, it can sometimes take many years to learn whether a drug actually provides a real effect on how a patient survives, feels, or functions. A positive therapeutic effect that is clinically meaningful in the context of a given disease is known as clinical benefit.
Mindful of the fact that it may take an extended period of time to measure a drug’s intended clinical benefit, in 1992 FDA instituted the Accelerated Approval regulations. These regulations allowed drugs for serious conditions that filled an unmet medical need to be approved based on a surrogate end point. Using a surrogate endpoint enabled the FDA to approve these drugs faster.
A surrogate endpoint used for accelerated approval is a marker – a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit, but is not itself a measure of clinical benefit.
Likewise, an intermediate clinical end point is a measure of a therapeutic effect that is considered reasonably likely to predict the clinical benefit of a drug, such as an effect on irreversible morbidityand mortality (IMM).
Accelerated Approval can be applied to promising therapies that treat a serious or life-threatening condition and provide therapeutic benefit over available therapies.
This approval pathway is especially useful when the drug is meant to treat a disease whose course is long, and an extended period of time is needed to measure its effect. After the drug enters the market, the drug maker is required to conduct post marketing clinical trials to verify and describe the drug’s benefit.
Where confirmatory trials verify clinical benefit, FDA will generally terminate the requirement.
Approval of a drug may be withdrawn or the labeled indication of the drug changed if trials fail to verify clinical benefit or do not demonstrate sufficient clinical benefit to justify the risks associated with the drug (e.g., show a significantly smaller magnitude or duration of benefit than was anticipated based on the observed effect on the surrogate).
Since the Accelerated Approval pathway was established in 1992, many drugs that treat life-threatening diseases have successfully been brought to market this way and have made a significant impact on disease course.
For example, many anti retroviral drugs used to treat HIV/AIDS entered the market via accelerated approval, and subsequently altered the treatment paradigm. A number of targeted cancer fighting drugs also have come onto the market through this pathway.
Resource Person: BARBARA PIROLA