Most new drugs are denied by the Food and Drug Administration (FDA) because they lack adequate information from clinical trials, according to a new study published in JAMA. The study suggests that pharmaceutical companies can improve their strategies for drug development by submitting more thorough and sufficient information, thus speeding up the approval process. Currently, the process from clinical testing to approval takes an average of eight years, with only one in six drugs ultimately receiving approval. FDA delays and failures cost time, money, and ultimately the health of patients waiting for new treatments.

Leonard Sacks, associate director for clinical methodology at the FDA's Office of Medical Policy, and his colleagues at the Center for Drug Evaluation and Research looked at applications submitted between 2000 and 2012 for new molecular entities (NMES), or drugs containing ingredients never marketed in the United States. They analyzed letters, summaries, and reviews between the FDA and pharmaceutical companies to analyze why these NMEs were denied or delayed. The results show that while 222 of the 302 NME applications they reviewed were eventually approved, 151 had initially failed. Of these failures, 71 of the drugs took an average of 435 days to gain approval.

One common reason for initial failure included a lack of information about the optimal drug dose a patient should take to maximize its effect and minimize danger. Without an optimal dose, it’s hard to tell whether a drug is safe or not. Another common reason included unsatisfactory end points in clinical trials; end points are the goals by which the success of a drug is measured — like survival or response rate. The study also noted that drugs often failed because the populations studied in the trial didn’t reflect the populations most likely to take the drug.

When deficiencies like these are discovered late in drug development, they can increase the cost of development and delay patients from receiving innovative drugs.

“It is advantageous to identify products that fail as early as possible in the development process to avoid these issues,” the study authors wrote. “For those drugs that require resubmission before approval is obtained, delays are taxing on the industry and regulators, and patients may have to wait for access to promising, and sometimes lifesaving, new treatments.”

The authors push for a revamp of how clinical trials are designed — suggesting that delays and initial denials can be avoided if drug companies know what information the FDA requires to deem a drug safe and effective. “Early and frequent dialogue between the FDA and drug sponsors addressing critical aspects of study design (including the selection of study populations, study end points, and drug doses) has the potential to reduce delays in the approval of new drugs,” the report says.



Source: Sacks L. JAMA. 2014.