snake oil???

I have written a few recent blogs on the increasing laxity of regulation. One (see http://gmodestmedblogs.blogspot.com/2015/08/implantable-cardioverter-defibrillators.html  ) highlighted the use of implantable cardioverters, use of which has migrated from studies documenting benefit in less elderly stable ambulatory patients to implanting them in the unstudied older sick hospitalized ones, then finding no clear clinical benefit in this group. Another (see http://gmodestmedblogs.blogspot.com/2015/08/regulation-of-medical-devices.html ) looked at the approval process for medical devices, which involves minimalist premarket studies often to be followed by FDA-required aggressive post-marketing followup studies which are mostly never done/printed. In this light, there was a truly scary article in New Engl J of Medicine this week (see medication regulation dec NEJM2015 in dropbox, or DOI: 10.1056/NEJMhle1506365). This article reviews the history of the FDA, its developing much more teeth in 1962, and the erosion of its power over the past few decades, culminating in the current pharmaceutical case as below.

--the current case: in May 2015 Amarin (a small Irish drug company) sued the FDA to allow it to distribute information about the usefulness of its prescription fish oil product for an unapproved indication (lipid lowering), stating that such refusal violated its First Amendment right to free speech. The FDA replied in June with a conciliatory letter stating that most of the information was okay (also suggesting that the drug be reclassified as an unregulated dietary supplement... a topic for another blog). The company rejected that, went on with the lawsuit, and in August a federal judge sided with the drug company, citing its "'considered and firm view' that the FDA could not prevent promotion of a drug for an unapproved use if a manufacturer's promotional statements are 'truthful'". [note: one potential consequence is that patients might be prescribed fish oil for lipid management, without documented clinical benefit, instead of clinically-proven therapies. And, does a small drug company sponsored study showing some decrease in triglycerides qualify as "truthful" promotion for a clinical indication? And should that be determined in the court system?]

history (in very brief -- the article is quite good on this)

--FDA established in 1906

--until 1962, drug manufacturers were not required to demonstrate that a new drug worked

--1962 legislation: FDA was given authority to consider any drug labeling or promotional material that was not explicitly approved by the FDA as "false or misleading" and subject to fines. More than $15B in fines were levied starting in the early 2000s til the present against almost all of the drug companies for illegal off-label promotion (eg promoting use of antipsychotics in elderly with dementia to control behavior). the rationale for this legislation was that neither consumers nor physicians could be expected to determine drug effectiveness or safety without an extensive evaluation by the FDA scientists and advisors reviewing all the data

--the erosion of FDA authority seems to have begun in 1980 (which, by the way, was when Reagan was elected...), when the Supreme Court took on a case by compounding pharmacies trying to avoid governmental oversight, the Court finding that the government did have a substantial interest in promoting public health by ensuring rigorous drug testing but also had an interest in facilitating patient access to the drugs. [the recent series of 11 infectious outbreaks caused by contaminated compounded meds affecting 207 and killing 17 was attributed to "inadequate regulatory controls".]

--there have been other recent examples: a drug rep successfully sued the FDA that promoting an off-label indication for a drug (sodium oxybate) was infringing on his right to free speech.

--the FDA itself had been undercutting its own authority, and in Feb 2014 issued a draft guidance that would make it easier for drug companies to disseminated information about non-approved drug indications. This included allowing drug reps to distribute peer-reviewed studies that describe lower risks from the meds than what was determined by the FDA.

so, this brings up several issues:

--the potential further degradation of the quality of the data: those studies, for example, which might show fewer adverse drug effects than the FDA documented in their broad review will almost always be sponsored by the drug companies (with their attendant well-documented shenanigans).  and, even if those of us in the trenches were aggressively trying to assess all of the relevant studies, we do not have access to many of them -- esp the negative studies (though the FDA does)

-- a related issue mentioned in prior blogs: there is a huge concern with the large numbers of clinical guidelines, with a dramatic shift from governmentally- generated (eg NIH) to specialty society sponsored ones.  a JAMA study (JAMA 2009; 301: 831-41) found that of 16 guidelines released by the Am College of Cardiol and Am Heart Assn, 1/2 of the recommendations had evidence level C (expert opinion), and a large % of the guideline writers (ie, experts) have significant conflicts of interest. (i am not just picking on cardiology -- there are similar issues with lots of other specialty recommendations). A viewpoint in the Sept 1 2015 issue of JAMA notes that the Institute of Medicine considers the current approach to the development of clinical practice guidelines to be very flawed, in part from these often-unreported conflicts of interest. this is another issue diluting our ability to practice the highest quality medicine based on the best evidence.

--and, the big issue: further erosion of FDA regulatory power, perhaps under guise of free speech for corporations (now considered to be "personlike entities" by the 2010 Citizens United case) could bring us back to the snake oil salesmen of old, and that neither we as providers nor the patients might be able to evaluate the studies well (pretty much all done by drug companies), which would dramatically undercut our ability to make sure that the benefit of meds are real and outweighs their ris