Practical advice on disseminating off-label information: After WLF

A great cartoon shows a couple of Food and Drug Administration guys sitting at their desks, and one of them says to the other, "If laughter is really the best medicine, shouldn't we be regulating it?" When I joined the FDA's Division of Drug Marketing, Advertising and Communications in 1995, the FDA would not have laughed at that, because the attitudes toward First Amendment protection were not far from that expressed in the cartoon. The FDA actually had a policy that prohibited companies from disseminating published reprints. In 1995, the WLF case was already going on, and the attitude of the senior management at the FDA at that time was that they were going to file a motion for summary judgment and it was all just going to go away. As we know now, that did not happen, and when we got into the discovery phase, the FDA finally realized that as well. In just a few years we have come far from the FDA's position that the First Amendment protections did not apply at all to companies' speech about their products.

Judge Lamberth ruled that the FDA cannot proscribe the dissemination of reprints, as long as certain rules are followed. Where does Judge Lamberth's ruling stand today? The Appellate Court's decision noted that part of the injunction still stands. The FDA nevertheless maintains that the guidance documents were superseded by the FDA Marketing Act, and therefore the injunction is moot. However, Judge Lamberth was clear that his order applied to the policies underlying the FDA's guidance documents, and hence, WLF vs. Henney is still good law. If you look at the Appellate Decision, footnote 7, it states, "In disposing of the case in this manner we certainly do not criticize the reasoning or conclusions of the District Court. As we have made clear, we do not reach the merits of the District Court's First Amendment holdings and part of its injunction still stands."

It was clear from Judge Lamberth's various rulings that his injunction and order applied not necessarily to the guidances but to the underlying policies, and that the FDA cannot restrict speech simply because the data at issue have not been reviewed by the FDA. But discussions with people at the FDA make it clear that their attitude is that Judge Lamberth's order applied to the guidances. The guidances are now superseded by FDAMA, and the FDA's view is that Judge Lamberth's order simply does not exist. This is evinced by the fact that the judge's order was not mentioned in the Federal Register notice issued by the FDA in March 2000, in which it stated its position on the Appellate Court's decision. It is not surprising that WLF is going to go back into court. Given what Lamberth has said in the past, and given the FDA's intransigent attitude about his previous orders, I believe he will deal severely with the FDA yet again.

There will probably be another injunction or an amended order in the not-too-distant future, which the FDA will be under. Then the FDA will go up on appeal, and the process will begin again. In the meantime, I choose to believe that Judge Lamberth's order is still in effect, and that the FDA may not proscribe dissemination of reprints, so long as they are disseminated within the boundaries of the order. I think that most of the industry is disseminating reprints in accordance with the judge's order.

I strongly recommend that if you are going to disseminate reprints, you do so very carefully. In-house counsel or the regulatory affairs department must establish internal procedures for reviewing and approving the dissemination of these reprints in the same way your company would review and approve any other piece of promotional labeling. If your company does not have a process like that, it is asking for trouble.

Distribute only peer-reviewed, original articles. Judge Lamberth's ruling provides some very good opportunities for disseminating scientific literature, but the industry as a whole needs to avoid ruining these opportunities by reprinting editorials and review articles. I recommend that companies stick to disseminating reprints of original research articles and make sure that they are peer-reviewed. It may help to ask your regulatory department to call the publisher and ask some questions to ensure that a journal meets the accepted definition of "peer-reviewed."

Limit yourself to 'scientific exchange.' Scientific exchange includes promotion of an investigational new drug, dissemination of off-label reprints and texts, and answers to unsolicited requests for information. Regarding promotion of an investigational new drug, the Code of Federal Regulations says, "A sponsor or investigator ... shall not represent in a promotional context that an investigational new drug is safe or effective for the purposes for which it is under investigation or otherwise promote the drug. This provision is not intended to restrict the full exchange of scientific information concerning the drug, including dissemination of scientific findings in scientific or lay media. Rather, its intent is to restrict promotional claims of safety or effectiveness of the drug for a use for which it is under investigation ..."

Judge Lamberth clearly said that companies may not initiate person-to-person discussions about off-label uses. On the other hand, he said companies can disseminate reprints to physicians. In my view, if you follow Judge Lamberth to the letter, and you do not say anything that is not in the reprint, then you are engaging in the dissemination of scientific literature. Again, in my view, this falls under the rubric of scientific exchange and is a constitutionally protected activity, unless, of course, the FDA can meet its burden of showing that the information is actually false or misleading.

Include a package insert with a reprint. There are very sound product liability reasons for including a package insert. If a doctor admits that he read the package insert and was fully familiar with all of the literature involving a drug, and not just the reprint you handed him, your company may not be liable in a product-liability case. Another consideration related to including a package insert is that you may be conceding that it is labeling.

Companies probably should err on the side of caution and include the package insert. The issue becomes somewhat moot in the real world, because many companies have a policy that on any sales call, the representatives are to leave a package insert for whatever product they are discussing.

Answer only unsolicited questions within the bounds of the reprint. Sales representatives should be allowed to respond to unsolicited questions regarding the material. The FDA opined on that in the preamble to the final rule, when they codified FDAMA in 21 CFR, Part 99, stating, "Although FDA does not construe Section 557(a) of the Act as a specific legal authorization for manufacturers to provide off-label use information to healthcare practitioners in response to an unsolicited request, Section 99.1(b) of the final rule recognizes this statutory provision." This was issued when WLF was still pending. The FDA apparently views the sales representative/physician encounter as an inherently coercive atmosphere. My inclination is to ignore this whole discussion preamble, and to take the section of FDAMA at its face value, which is that if it is truly an unsolicited request, anything a physician asks a drug company can be answered, whether it is off-label or not.

Inevitably sales representatives ask, "What can I do with this reprint? Headquarters has approved it, I have been given 250 of them, and I am supposed to hand them out. What can I do, and what can I not do?" I tell sales reps that they can hand the reprint to the doctor, and if he or she asks a question about it they can answer that question, as long as the answer remains within the bounds of what is contained in that reprint.

Once a doctor starts asking questions actively, the company is entering into safe territory, because now the physician is actively seeking out the information. The answer to a doctor should be: "This is a study involving X number of patients, that evaluated Drug A versus placebo, and the study showed this. If you want any further information I will have our medical affairs department send it to you." In an enforcement action, the fact that the doctor may have been asking for the information could be used as a defense by the company, and the FDA would have to meet the burden of showing that the company went beyond what Judge Lamberth allows. But sales representatives should minimize extraneous comments that might fall into the hands of a plaintiff's lawyer.

In 1998, the first WLF case regarding the FDA's policies on dissemination of information on off-label uses of drugs concluded that First Amendment protections do apply to companies' speech about their products. Considering its previous policies on the subject, the FDA was taken aback by the decision. Yet, the situation has evolved, and today uncertainty surrounds the Appellate Court's ruling in the most recent case dealing with dissemination of information on off-label uses; companies should tread lightly. PR