Understanding what is required in a clinical trial for approval by the US Food and Drug Administration (FDA) when bringing a particular drug to market can help researchers avoid challenges later on in the process.
The FDA approval process requires the assurance of 3 elements: efficacy of the product, safety of the product, and demonstration of the ability to manufacture a quality product reproducibly. That being said, the current system is time consuming and costly, Errol Gould, PhD, director of Medical Affairs at Pernix Therapeutics, told the crowd at PAINWeek.
According to studies he cited, it takes 12 to 15 years for a drug to move from discovery to market,1 and the cost to develop a new pharmaceutical drug can exceed $2.6 billion.2 Additionally, approximately 1 in 10 molecules tested in humans reaches the market.3
The FDA approval process itself goes through several stages: chemistry and discovery, pharmacology and safety, clinical trials, and ultimately market.
Dr. Gould stresses that it is important to remember that there is a range of clinical trial designs available that demonstrate both the safety and efficacy of medications.
Clinical study designs used for approval of a new medication are typically based on precedent. There are more than enough study designs to choose from: superiority, equivalence, noninferiority, crossover, dual crossover, enriched enrollment randomized withdrawal, combination rule, and adaptive design.
“Study design selection is often based on historical information obtained from the prescribing information of medications in the same drug class and published literature, or after discussions with the FDA,” Dr. Gould said.
Dr. Gould advises that it is important to remember that several differences exist between superiority and noninferiority studies. The former requires no further extra-study information, as the result speaks for itself. Noninferiority studies, however, are dependent on the investigators knowing something that has not been measured in the study.
Adaptive designed studies are multistaged studies that use accumulated data to modify one or more aspects of a study without undermining the validity and integrity of the trial. Several aspects of the study can be modified; treatment doses, number of treatment arms, randomization proportions, and maximum sample size represent a sampling of modifiable study design characteristics.
Researchers are given the ability to select which study design they’d like to use for a given report. The decision usually depends on what they believe will work best for what they are trying to accomplish.
“The FDA does not dictate which study design is required for approval,” Dr. Gould explained.
Adaptation can be appropriate when outcomes are available rapidly in relation to the time course of the trial, or when there is substantial uncertainty regarding relative efficacy or adverse event rates.
“Clinical trials are designed to meet the requirements set forth by the FDA that the medication is both efficacious and generally well tolerated,” he said. “This typically means that some patients are treated with a placebo.
A challenge to investigators when considering a clinical trial focused on pain is that the trial design may differ markedly from actual clinical practice. In the point-of-care setting, patients are not typically subjected to the possibility of receiving a placebo as part of their treatment plan. However, in pain clinical trials, patients are often prohibited from having their medication dose changed during the double-blind treatment period.
“In clinical practice the patient’s dose or even the medication will be changed if the patient is having adverse events or not responding well,” Dr. Gould explains.