i-eclectica.org

The New Scientist published an article by Paula Caplan and Emily Cohen who both claim that a lack of proper safety guidelines in the US does not engender trust in the development of drugs by pharmaceutical companies.

A major reason they don’t is that the FDA’s guidelines for research into new medicines contain serious flaws. To highlight them, Caplan and Cohen focus on antidepressants, which are not just top-selling drugs but also an example for how the pharmaceutical industry has regularly concealed negative effects. And US legislators and the FDA have made it easy for the drug companies to behave unethically. “It is 30 years since the FDA published the current guidelines for research into antidepressants. They were scheduled for review every 18 to 24 months, but the 1977 version is still all there is.”

The way the regulations are written makes you wonder who was the ghostwriter behind the scenes. For example: there is no essential symptom list for depression on which clinical trials can be based on; participants are only required to show four or five “associated symptoms”. This lack of stringent criteria of course lightens the burden on the shoulders of drug companies’ executives; trial management becomes easy when the legal framework theoretically allows for non-depressed individuals to be recruited and for “genuinely depressed patients with, say, three severe symptoms [to be] left out”. But there is more:

• “the guidelines say subjects whose clinical condition worsens or fails to improve ‘in a reasonable period of time’ are to be removed from the study, but drug companies need not include data about them in their statistical analyses”;  this inflates drug’s effectiveness and minimises its negative effects
• “the guidelines state that clinical trials should last for around four to six weeks”; often though drugs may take much longer for example to produce negative effects; equally the short trial length might “fail to pick up the many people for whom psychotropic drugs are initially helpful but later ineffective”
• “similarly, the FDA recommends that drug companies monitor trial participants for at least one week after they stop taking the drug, yet it may take longer than that for withdrawal symptoms to emerge”
• “evidence for safety and efficacy is acquired over the course of many studies carried out over considerable periods of time and at different geographical locations” - a very vague ‘guideline’ for the efficient collection of robust safety data, especially since the guidelines “require neither that all the findings are pooled together nor that the research be overseen by an independent regulator”
• “women of childbearing potential, children and individuals with serious diseases” should be excluded from the research, which sounds rather absurd given that many people in these groups are regularly prescribed antidepressants; in addition it is not rare that “some women take antidepressants throughout pregnancy, even though the FDA says that long-term safety studies need last no more than three to six months”

According to the article, the points made above do not just represent theoretical risks; there are apparently “plenty of indications that all is not well”. Two examples mentioned are the drugs Avandia and Prozac, where the FDA failed to act despite its European counterpart EMEA strengthening its warning about the risks these drug carry. It seems that it is not only time “for a full review of FDA research guidelines for all categories of drugs” (as the  article suggests) but also for a thorough investigation into the the possibly cozy relationship between FDA and drug companies.