Darshan: Hey, everyone. Welcome to another episode of Darshan Talks. We have a very, very special guest for you. We've got Dale Cook and Dale Cook is the guy you talk to when it comes to promotional compliance. I do a bunch of work in it. He does a bunch of work in it. We talk a lot about this. He's the guy I've always reached out to and we have a camaraderie going. So I have this great opportunity for us to talk and learn more from him.
Intro This is the DarshanTalks Podcast, Regulatory Guy, Irregular Podcast with host Darshan Kulkarni. You can find the show on Twitter @darshantalks or the show's website @darshantalks.com.
Darshan: Dale, do you want to introduce yourself a little bit?
Dale: Sure. Thanks, Darshan for having me on. I've been following your podcast since you launched it. I'm really glad that we were able to work out some time to have this discussion, and I appreciate you opening up your audience.
Dale: I am an FDA regulatory consultant. I started my independent practice five years ago. The tagline I use associated with my company is I help companies use 21st century technologies while communicating about FDA regulated products. And remaining compliant with regulations written in the 1960s. That core challenge of the Regs themselves have not changed and there are good aspects of that, right? We don't want the Regs constantly changing, but the world in which we live is very, very different from the world in which those Regs were written. And that is that mismatch between the world for which they were written and the world in which we actually wake up every day, I think presents one of the challenges for the companies that you and I both advise.
Darshan: So that really brings us to the first question of, Regs changing and one of the areas that Regs are, well, not the Regs but the laws are changing, is in the area of compliance and in the area of off-label compliance specifically. Before we go down that path, the real question is what does, well, let's start with what is on-label, first of all? What does the word label mean? How is that different from labeling and why does any of this matter?
Dale: Right. Yeah, so I mean the major significant radical change in the law in the 1960s going back to the Kefauver Harris hearings, was this notion that companies had to demonstrate that products were safe and effective prior to bringing the product to market as a new drug. And so if you create, invent, discover a new drug, you have to demonstrate to the FDA prior to introducing it to market that it's effective. The minute you do that, the minute you introduce that concept, you have to get the for what, right? Effective for what?
Dale: And that introduces the idea of an indication. So your product doesn't get introduced to the market tout court, it's on the market you can do whatever you want with it. You may only introduce it into the marketplace for those specific indications where you have demonstrated to the FDA that the product is safe and effective.
Dale: So that's the concept of an on-label use. An on-label use of a product is any use of the product where the company has, in fact, demonstrated that it is safe and effective and they have the labeling approved by the FDA for such use.
Dale: And then off-label use is anything else, right? Anything else, meaning in a different patient population. The vast majority of drugs come on the market only indicated for use in adults, but of course children get ill too. So pediatricians are constantly faced with the challenge of using new products when they're using them probably in an off-label manner. Using them in an elderly population. Frequently you exclude pregnant women from your clinical trials for various reasons. But pregnant women also get prescribed medications.
Darshan: Mm-hmm (affirmative).
Dale: So there are tons of off-label uses that are going on. Not to mention, one of the biggest types of off-label use where there simply is no FDA approved product. By definition, when there is no FDA approved product for a specific patient or a specific condition, then anything that their prescriber, their healthcare professional does is going to be off-label. So off-label use is not necessarily a scary, bad thing, but off-label promotion can essentially [crosstalk 00:05:01] these open.
Darshan: Hold on. Before we get into off-label promotion, you said it's not a scary, bad thing, but doesn't off-label use necessarily mean that it's not been FDA approved? Therefore it is a use that Pharma companies are pushing onto physicians, and therefore it is inappropriate, and therefore the use is... There's no proof that it actually works, and therefore these patients are being preyed upon and it's just physicians in big Pharma's pocket. What about your response to each of those?
Dale: Yeah. So, no. There certainly are cases where off-label promotion and use has been pushed to the detriment of patients and to put patients at harm.
Dale: But there absolutely are places where off-label use is quite literally the standard of care. Where you have, for example, clinical practice guidelines put out by reputable organizations, that direct physicians to use certain products in ways that have not actually been approved by the FDA. And that could be either because the company is currently in the process of seeking the approval from the FDA for those uses. Or it could be the case that the company has never had the financial incentive to go out and to pursue the approval for those uses. Maybe it's not a big enough market or something like that. The product is too old. It's no longer going to be under patent protection. So they don't have those financial incentives to do it.
Dale: So yeah, there can be off-label use that genuinely puts patients at risk. But just the fact that something is off-label use doesn't automatically mean that the physician or anybody else is doing something inappropriate. It can be, in fact in some cases, if you're a physician and you're not using a product off-label, you can be opening yourself up to medical liability for not actually doing the thing that every other healthcare professional would do with a patient in that type of a setting.
Darshan: So is that evidence that physicians are just in big Pharma's pocket? That if they don't follow the requirements they might be exposing themselves to liability because they're prescribing a drug off-label then?
Dale: Well, I mean I wouldn't say that that means that physicians are in big Pharma's pocket. I would say that that means that the practice of medicine is independent of FDA Regulations. And sometimes the practice of medicine is proceeding at a far more rapid pace, and developing in ways that it's just not possible for FDA's labeling requirements to keep up with.
Darshan: Fair enough. And now then you were talking about the distinction between off-label use and off-label promotion. So please, go ahead.
Dale: Right. Yeah, so off-label use is any use of an FDA approved product that's not in accordance with the FDA's label. We talked about several different examples used in different patient populations. The [inaudible 00:08:22] approved label, such as the classic using a child when you don't have a pediatric indication.
Dale: Also used for a different disease state. Again, when you're dealing with a patient who has a condition or which there is currently no FDA approved use, then any use of any product is, by definition, going to be off-label with that patient. And certainly, when we have an oncologist who's faced with a patient who's going to die in a few months unless they receive some form of treatment, we don't want that oncologist to say, "Well, I can't do anything for this patient because there's no FDA approved use."
Dale: So that's the use. And as I say, there certainly are times when off-label use can be inappropriate. But there are lots of times when off-label use is completely acceptable and appropriate.
Dale: Off-label promotion is when the pharmaceutical company is aware of the off-label use and engages in activities to encourage physicians to engage in that off-label use. And that is what potentially opens up people to significant liability.
Darshan: Okay. So, why does it open people up to significant liability? You just talked about how it's important, how it could be a standard of care, how it may help babies. I mean those all sound like great things.
Dale: Yes, helping babies is a good thing and we're all in favor of it, right? But off-label promotion, the problem is there's no law. There's no sentence in the Food, Drug and Cosmetic Act that says off-label promotion is illegal. There's no sentence in the Food, Drug and Cosmetic Act that says off-label promotion subjects the person engaging in it to five years in jail.
Dale: But the government's theory of the case that they've used in a lot of these cases is that engaging in off-label promotion violates one of several different provisions in the Food, Drug and Cosmetic Act. Potentially it involves a violation of introducing a misbranded drug. That you're introducing a drug into the marketplace without providing adequate directions for use of the product. That because you're talking about a use that's outside of the approved product's label that you then have not provided the adequate directions for use that are required. Or, potentially you're engaged in introducing an adulterated product into the marketplace because you haven't provided sufficient information and received the approvals in advance.
Dale: So, it's an indirect form of enforcement and the specific facts of the case or what the government then uses to put forward one of its few different theories. And it would be inappropriate for me to avoid mentioning or to neglect to mention the potential implications for the False Claims Act.
Dale: False Claims Act enables the government to recover for any reimbursement of healthcare where a false claim is submitted. If there is a false statement made by a pharmaceutical company as part of its promotion, and that false statement leads to, induces in some way, the physician to submit a reimbursement for the healthcare services, then that opens up the company that made the false statement to false claims liability. And that's where you get some of the huge, huge fines and settlements where the companies agree to pay hundreds of millions, or in some cases even billions of dollars to settle those false claims allegations.
Dale: So it's a complicated story as to why off-label promotion is as scary as it is for companies. But there are lots of different avenues and paths that can present significant liability, both civil and criminal for the companies and the individual executives engaged in off-label promotion.
Darshan: Great. Now stay tuned. We're going to have Dale come back, talk to us in another podcast and we're going to start getting into some details. And details is where this stuff gets really, really fun. So stay tuned.
Outro This is the Darshan Talks Podcast. Regulatory Guy, Irregular Podcast with host Darshan Kulkarni. You can find the show on twitter @darshantalks or the show's website at darshantalks.com.[/learn_more]