Expedited review of new drugs by the FDA is being questioned.
WASHINGTON - New drugs that receive expedited review by the Food and Drug Administration are being tested on fewer patients, leaving many safety questions unanswered even after they are approved, a study released on Monday in the Journal of the American Medical Association found.
Study authors Thomas Moore of the Institute for Safe Medication Practices and Dr Curt Furberg, a professor at Wake Forest School of Medicine, examined the development times, clinical testing and risks associated with 20 new drugs approved in 2008. Eight were given expedited review and 12 standard review.
It found that expedited drugs underwent a median of 5.1 years of clinical testing before being approved, compared with 7.5 years for those that underwent a standard review. But in many cases safety monitoring trials that were supposed to be conducted after the products were approved were either not conducted, not completed or not submitted to the FDA.
"The testing of new drugs has shifted from a situation in which most testing was conducted prior to initial approval to a situation in which many innovative drugs are more rapidly approved after a small trial in a narrower patient population with extensive additional testing conducted after approval," the authors said.
At the urging of patient groups, Congress and the drug industry, the FDA over the past decade has introduced multiple mechanisms for speeding new products to the market. While patient groups and drug companies applaud these measures, saying they get much-needed medication into the hands of patients more quickly, critics say the agency is approving products before they have been fully vetted.
Of the drugs studied by Moore and Furberg in 2008, the FDA required 85 follow-up trials to monitor for safety. By 2013, only 40 percent of those studies had been completed.
The FDA said in a statement that it will review the article in more detail but that on the surface "it shows that the expedited development programs are working as intended by getting promising new drugs to patients more quickly."
The FDA has traditionally required two controlled clinical trials to prove that a drug is safe and effective. Over time, the agency has relaxed the evidence it is willing to accept for certain products.
In some cases the FDA will accept data from a single trial and success may be judged on the basis of a surrogate measure - such as tumor shrinkage - that may or may not translate into a concrete measure such as increased survival.
"In situations of serious and life-threatening diseases with unmet medical need, patients and physicians who treat them have told us repeatedly that they are willing to accept greater uncertainty about risk in order to have access to the hope of improved treatment today," the FDA said in its statement.
The FDA is discussing additional measures to speed the drug development process, including the use of "enriched" trials that would select patients based on certain demographic or genetic characteristics in order to increase the chance of a trial's success.
The idea is to direct treatment to patients for whom it will be most effective or who are most likely to respond.
But in a commentary published alongside the study, Daniel Carpenter, a professor of government at Harvard University, said the FDA has put few measures in place to ensure that drugs that are approved based on limited populations are only marketed to those limited groups.
"The current system of accelerating drug approval in the United States can be described as a growing hodgepodge of exceptions to the rule of rigorous premarket review," he said.
The FDA said it has a "robust program for postmarketing surveillance and ensuring the completion of required post-approval trials."
"We believe that we have set the bar for the balance between pre-approval testing and early availability of promising new drugs to treat serious and life-threatening diseases in the right place."
First published October 28 2013, 3:45 PM