The clamor for additional or lengthier studies to detect safety signals often prompts rejoinders that such efforts would not only lengthen the amount of time before a medicine could hit the market, but also adds to the development cost, which would be passed along to purchasers. Just the same, a new study indicates the number of patients needed to study chronic use in the European Union is insufficient to evaluate safety and long-term efficacy.
Consequently, the researchers say that a "reevaluation" of both the number of patients participating in clinical trials and the long-term requirements for collecting pertinent data for regulatory approval of new medicines is merited. And this is especially true for drugs that are designed for long-term use.
The study analyzed data from studies submitted to the European Medicines Agency regarding 200 drugs that were approved between 2000 and 2010, and whether the number of patients was in sync with guidelines issued by the International Conference on Harmonisation E1. This is also followed by the US for determining trial sizes need for safety of drugs to be used on a long-term basis for illnesses that are not life-threatening (see this).
The study, which was published in PLos Medicine, found that the median number of patients studied before approval was 1,708 for standard medicines and 438 for orphan drugs. On average, chronic meds were studied in a larger number of patients - the median was 2,338 - than drugs for intermediate or short-term use - 878 and 1,315, respectively.
Also, the safety and efficacy of chronic use was studied in fewer than 1,000 patients for at least six and 12 months in 46 percent and 58 percent of new medicines, respectively. Among the 84 medicines intended for chronic use, 68, or 82 percent, met the guideline recommendations for 6-month use, while 67, or roughly 80 percent, of the medicines met the criteria for 12-month patient exposure (here is the study).
And so, the researchers conclude that "the numbers of individuals studied before approval of new medicines in Europe from 2000 to 2010 are... generally adequate to assess only short-term efficacy. For most approved medicines intended for chronic use, the number of patients studied before marketing is insufficient to study safety and long-term efficacy... A discussion of the long-term exposure requirements for approval of medicines, particularly for medicines intended for chronic use, seems warranted." Whether any meaningful conversations will take place is unclear. Certainly, the findings underscore the ongoing tension between those who want more drugs to be available as fast as possible - a diverse group that can include most any type of stakeholder group - and those who maintain that haste makes waste, and also sometimes serious adverse events. But the findings suggest there is a price to pay when studies do not gather enough information for the long haul. In other words, short-term gain, but long-term pain.
confused pic thx to guudmorning on flickr