Good Reprint Practices

According to the Pink Sheet, Ann Witt a former Acting Director of DDMAC (or its predecessor organization, I can’t remember the name) is returning to the FDA in CDER’s Office of Policy, Planning and Budget.  Ms. Witt was a key staffer for Waxman, who you might recall very vocally questioned the substance and guidance making process for FDA’s Good Reprint Practices guidance document.  I recall hearing Ms. Witt last year speak an an FDLI conference where she was very articulate about her opposition to the Guidance document. Her concerns were obvious– off-label promotion and pharma influence on policy.

Who knows how this might affect DDMAC’s enforcement policy in the future.  Its unclear to me what role Ms. Witt will be taking.  I will say this though, FDA’s guidance document remains a difficult document to use prolifically.  If you read the plain mechanical language of this guidance document and try to comply with it, it won’t lead to a waterfall of off-label reprints (at least under this guidance).  And remember, to the extent that FDA provided a safe harbor from following the guidance document, you still have to comply with the four corners of the document to claim any off-label promotion safe harbor.  FDA’s record of such a strict reading of the safe harbor stretches back to FDAMA 401 and the WLF.  If it complies, FDA will not use it as evidence of misbranding–if it doesn’t comply they reserve the right to use it as evidence of misbranding.

Nonetheless, I would expect this key Waxman staffer to have a significant impact on FDA’s policies in one way or another.

Regards,

John Murray

In an untitled letter dated April 16, 2009, FDA’s Division of Drug Marketing, Advertising and Communications warned Sanofi Aventis about what it alleges are unsubstantiated claims about the oncology product Taxotere on a reprint carrier.  The letter includes fairly common objections of unsubstantiated superiority claims and overstatements of efficacy. For those of us practiced in the art, these are common themes in FDA’s enforcement record on drug advertising. 

In its letter, FDA focuses on the fact that the reprint itself reports results from a study in which the primary endpoint failed to reach statistical significance and the claims in the reprint carrier emanate from what FDA considers a failed study.  FDA also reiterates its position that superiority claims require TWO  adequate and well controlled studies (actually this FDA interpretation emanates from the plurality of language in the FDCA and implementing regulations-I’ve yet to find the “two” requirement explicitly in either–in fact FDA’s official interpretation of this in its guidance document is more qualified than the language used in FDA’s letter.) 

Nonetheless, the enforcement action is an interesting piece of information to those interested in reprint dissemination under FDA’s Good Reprint Practices Guidance.  In this case, the item itself (from what I can glean from the letter) is clearly a promotional reprint carrier, and even in the aftermath of the Washington Legal Foundation case, reprint carriers have been considered fair game for DDMAC enforcement in even the most industry-friendly interpretations of FDA’s authority to regulate peer-reviewed reprints.  (FDA did not post the reprint carrier itself on its website).  Interesting here though, is that FDA sticks to citing the reprint carrier itself, but not the reprint contained within it (which without doubt contains the same claims or information).  I always find these details interesting, because FDA experts, lawyers, etc. argue amongst ourselves about FDA’s authority to regulate bona fide peer reviewed publications even when they are disseminated by drug companies.  FDA clearly would argue that it has unlimited latitude.  In this current enforcement case I wouldn’t take too much comfort in the focus of the carrier versus the reprint.  Further, I’m seeing a more confident FDA enforcement approach and I wouldn’t be surprised to see FDA unhindered by the reprint/reprint carrier distinction in the future.  Further, with all of the controversies around publications in recent years, I’m not sure of the appetite for industry court cases involving reprints.  Nonetheless, as always…it depends on the facts and one’s knowledge of them.

Yours truly,

John

Friday, FDA’s Division of Drug Marketing, Advertising and Communications posted 14 untitled letters (enforcement actions) on its website that cited 14 different companies for inappropriate sponsored links/search results place on search engines like Google or Yahoo!  I would not ordinarily discuss this issue on GoodReprintPractices.com, but reprint dissemination is only a myopic picture of my practice, which includes broader work in regulation of advertising and promotion.  Further, because this is one of a handful of web sites/blogs that is actually written and run by a working regulatory professional, it’s only natural that I have something to say.

For years there has been no small amount of desire for a guidance from FDA on Internet promotion of prescription drugs.  This has intensified more recently, particularly in the blogosphere, where people like John Mack have been feverishly critical of FDA’s lack of substantive guidance.  The bulk of the new interest from industry has grown out of a desire for greater drug company participation in social media phenomena like YouTube, Twitter, Facebook, MySpace, Sermo, and so on.  FDA has said it is working on its approach to social media, or at least is thinking about its enforcement approach. FDA itself has tiptoed into social media with widgets, twitter alerts, podcasting, etc., particularly to issue information about drug safety or public health alerts.  You can hear the accusations of “double standard” echoing across the hills.  I would agree to some extent, but point out that FDA uses social media to advance its public health management mission, whereas (in large part) the desire from industry seems to pervade from a desire to market products.  This isn’t necessarily a bad or inherently irresponsible thing, but if you want to advance the dialogue you have to recognize the distinctions.  I bet you my left pinkie finger that FDA would be super receptive to drug company proposals to twitter about the availability of new risks of serious or fatal side effects.  I’m a guitar player so you know how important my left pinkie is.

Stepping back from all of the social media swirl though, we can see FDA addressing more conventional internet marketing approaches, that of the sponsored link that companies pay for and script in order to promote their websites when search engine users search certain “purchased” key words.  FDA likens the resulting paid/sponsored search results to be promotional material, similar to any other print advertising or even banner advertising.  In the 14 letters that FDA issued last week, FDA cited companies for combining terms or information that related to the efficacy or safety of their drug and the drug name itself.  By combining these elements, the search results themselves that are displayed to the search engine user need to include an adequate or full representation of the drug’s approved use or indication and risk information for fair balance.  According to FDA, these sponsored links cited in the letters failed to include the required information in one way or another.  See the image below.

As a technical matter, FDA appears to be on solid ground, but I want to point out a few things that come to mind when I look at these actions.

What is it?  Labeling or Advertising?

Historically, DDMAC has exercised immense discretion in its enforcement.  They are an organization with far fewer resources than the combined resources wielded by the industry that they regulate.  It is reasonable and responsible for them to engage in targeted enforcement.  It is also reasonable for them and expected of them to interpret gray areas of the law and regulations.  That said, DDMAC cites its jurisdiction over these sponsored links by reference to the regulations found in 21 CFR § 200, 21 CFR § 201, and 21 CFR § 202 that relate to reminder labeling or advertising.  FDA does not cite which individual regulation applies, because DDMAC itself has not concluded which one applies.  Rather, DDMAC cites all three sections of the regulations on the basis that one of them must apply, but DDMAC has not made any official determination that the internet is “advertising” or “labeling.”  Instead, FDA just considers it to be “promotion” and throws it into a bucket that includes anything that resembles advertising, and then regulates it under advertising or labeling regulations.

I don’t criticize the authors of the letters.  There is no doubt that the sponsored links are meant to promote something.  But, isn’t it precisely because FDA can’t decide if the internet is advertising or labeling, that FDA should be issuing guidance or engaging in new rule making to clarify these issues for industry?

Is it unreasonable for drug companies to be confused about what FDA’s perspective was on these sponsored links?

Was the content of these sponsored links really irresponsible?  Is it reasonable to assume that someone using search engines in the year 2009 is eminently capable of clicking on the link and being redirected within the flash of an eye to a place where all of the things that were “omitted” are on display?  Is a sponsored link that says “Learn about Drug x for disease y” really an irresponsible communication causing a public health issue?

One solution to the issue is to provide a teaser, but without mentioning the name of the product for which the sponsored link is related to.  This would avoid the violation in most circumstances.  However, would people consider it deceptive to not disclose the product or what it is for?    By making the site a dummy URL like “ProductFacts.com” you’ll utimately be accused of being deceptive for not disclosing where you are actually directing the viewer to.  Is that really where we should be?  In the absence of industry sponsored results, you’re far more liable to get a pale full of links for snake oil supplements, attorneys, offshore pharmacies, and quacks.

The Irony and the Ecstasy

Maybe, just maybe, and most importantly, maybe most-est importantly…do we really know where the “ad” begins and where the “ad” ends when it comes to the internet?  Are the sponsored links really as disconnected from the website to which they refer?  The website exists without the sponsored links, but the sponsored links are fully dependent on the link to the website.  After all, much as we’d like to believe, the content on these different sites (the Google search engine and the drug website) don’t really exist in different “places” on the internet.  They simply exist in a web of connected code.  You can’t drive to drugproduct.com from Google.com.  You can click a couple buttons and cause things to appear on your screen, but if you are on the internet, you are on the internet.  That’s where you are and that’s where you stay (but not really…you’re not really there on the internet…you’re sitting somewhere looking at a computer screen…you’re on your butt). If you can access the Google search results you can access the product website with no difference in effort.  They aren’t in different places, they’re just pieces of code that are dependently connected.  These sponsored links were not ads in a medical journal for which the labeling is somewhere out in the drug distribution channel accompanying a stock bottle of pills.  Where would I have gone if I never left my desk chair, but I clicked on two different spots on my computer screen?

You could, I  suppose, argue that the information is stored somewhere on a server and that is a “place.”  However, when you are viewing a webpage, it is distributed at your computer screen.  What you see is where it’s at.  For instance, you don’t say that an advertisement in the newspaper exists at the printer or even at the company headquarters of the company sponsoring the ad.  It’s in the newspaper in front of you, regardless of where it was printed or where the company exists who paid for it.

I know these are the kind of questions you might get in college philosophy or physics classes, but it seems to me that we’ve all ironically come to believe in “virtual” reality, when in fact the reality is actually something different when it comes to the internet.  It’s actually not at all what it is designed to make you perceive.  That’s why they call it a virtual world.  The irony of ironies is that the application of FDA’s regulatory interpretation actually reinforces the unreal (and in fact, misleading) impression that the sponsored link and the destination website are in two different places.  They’re not.  In fact, neither of them really exist at all.  Sleep on that.

Let me say that I know people at DDMAC.  I think they are smart, and they have vital role.  Anybody who knows me as well, knows I’m no apologist for industry either.  But, I’m fascinated and perhaps perplexed by FDA’s recent approach.  I’m thinking out loud, and I may change my mind or have a clearer opinion in the future, but for now I’m wondering about everything I’ve written, and I’m hoping that we get to a better place in the future.  I’ve discussed the possibly of how these recent events have highlighted a need for an internet guidance or social media guidance from FDA.  I think there is some basis for that, but not for all of the reasons that so many have been thirsting for it lately.  I’m a realist.  I don’t think that FDA would want to drink from the firehose of new media ideas, but I think that the internet can be a place where both responsible and irresponsible healthcare communication can take place.  The internet itself is desperate for models of responsible healthcare communication that can truly identify and parse out detrimental self interest.  Not all self interest is bad, but should raise some levels of suspicion, particularly if you are a regulator.  It is in the collective self interest that we develop a communication model that is inherently responsible, transparent, and high quality–not just a clever way to market.  It needs to meet all these ends before FDA will have the self interest to open the door to the unpredictable.

Sincerely,

John Murray

It’s not lost on me that I’ve been taking a long time to get through my analysis of the Good Reprint Practices guidance.  My first problem is that I’m busy with other things, which in most cases, is a really good thing.  My second problem is that I sometimes go on fantastic voyages into the simplest of details.  However, I can’t stress enough that even the subtlest of details of this guidance should not be oversimplified.  On the other hand my goal is to be helpful, and not to drown my readers in complexities, that no matter how thoughtful and accurate, are incomprehensible and useless.

All that said, as I examine the basic requirements of reprints disseminated under this guidance, I feel inspired to highlight some very important language that needs to be considered carefully.  Some of the more basic elements of the guidance are straight forward. 

The Basics

When FDA explains the types of articles that can be distributed under this guidance, it starts with an explanation of the types of publications from which the individual articles can be taken, essentially peer-reviewed medical journals and “textbook” reference publications (published independent of manufacturers and commercially available for sale).  For this post I’m focusing on journal reprints.  In FDA’s final “Good Reprint Practices” guidance document, the basic nature of journal reprints can be summarized as follows.  They must come from medical journals that have the following characteristics:

1.     An editorial board that is expert in the specific subject matter of the article, and be able to independently review, objectively select, reject or comment on the articles that are published in the journal.

2.     The journal must have publicly stated policies (and must adhere to), full disclosure of any conflicts of interest or biases of study authors, contributors, or editors with the journal or organization.

3.     Be peer reviewed in accordance with the procedures of the organization; and

4.     Not be a manufacturer-funded supplement

Historically, these are well understood to mean that the journals from which articles come are peer-reviewed publications with typical scientifically rigorous editorial standards.  Think, New England Journal of Medicine, Journal of the American Medical Association …CONTINUE READING ARTICLE