While the happy victory of the court decision in Bayer v. US (FTC) still rings in our ears, business marches on, and we ask: How do we integrate elements of the court decision regarding adequate scientific substantiation into our own decision making? Even without it being mandated, two randomized, controlled trials had been the de facto highest standard for those wishing to err heavily on the side of conservatism regarding their claim substantiation risk. This recent ruling may seem to “give permission” to drop this high standard, but should that be the case?
Let’s examine two resources that can help us as we move into the “after” of this story, during which it may be possible that the top line of the decision becomes the bottom line in an inaccurate way.
First, let's look at the FTC standards themselves and what they mean.
The recent court decision “reinstated,” so to speak, the 2001 FTC guidance document called, “Dietary Supplements: An Advertising Guide for Industry,” as the standard that governs the use of claims in dietary supplement advertisements. At the same time, the two RCT requirement that has in the recent past been applied in selective cases was thereby struck down as a newly required standard across the board.
A large piece of the court decision was based on the principle in this guidance that flexibility is allowed in the types and nature of studies used to substantiate claims. The standard to meet is described as, “competent and reliable scientific evidence.” In practice, what this ultimately means is: the strength of the totality of the evidence. And what that means is a careful review of all the relevant literature to form an overall picture of what is known and with what level of strength. This is well-illustrated in the numerous examples in the guidance describing various combinations of study types, designs, qualities and similarities to the product in question, and whether they do or do not constitute sufficient substantiation.
And now the second resource: the FDA standards.
While FDA and FTC work together regarding claims enforcement, the FDA has its own focus and its own set of standards. These apply to labels and, “extensions of the label,” which include websites, shelf talkers, trade show collateral, social media and other communication vehicles. While the FTC standard for substantiation of claims used in advertising is “competent and reliable scientific evidence,” the FDA standard for substantiation of claims used on labeling is described as “significant scientific agreement."
It is well worth reminding ourselves at this time that FDA’s interpretation of this standard is discussed in another guidance document that came out in 2009, called, “Guidance for Industry: Evidence-Based Review System for the Scientific Evaluation of Health Claims.” This guidance records in fine detail the FDA’s own process for evaluating science as substantiation for structure function (and qualified health) claims, discussing many kinds of studies, levels of quality and a concept it calls “quantity of evidence for and against the claim,” and how these things all contribute (or do not contribute) to substantiation of label claims. FDA then determines whether the SSA standard has been met, “after assessing the totality of the scientific evidence.”
So here again we have the “totality of the evidence” concept as the core mechanism for determining the level of substantiation.
Both guidance documents covering advertising and labeling give us a clear indication of the path to be followed when designing claims and examining the evidence for them. They do not require two RCTs, and in fact, do not even encourage two RCTs. They ask and allow for all relevant, quality data that can help understand the picture and convince someone who is an expert in the field that the claim the data are supporting is truthful.
So, one who is evaluating that folder of evidence has to perform a critical weighing and balancing of each study, and then of the full picture given by the credible studies. Often there are holes in the knowledge, and these can weaken the argument, but sometimes they can be mitigated by other strong evidence.
Which brings me to the role of RCTs in the whole scenario. When one is trying to use the scientific evidence to make the case for a claim, having RCTs sure helps to make a strong one. Indeed, both guidance documents clearly state that well-controlled human clinical studies are the “strongest” and “most reliable” form of evidence. This is because the nature of the study design, when used properly, can provide data that makes it very clear that the benefits being claimed are real. Much of the time, other types of studies are simply not as powerful. Not having well-performed RCTs not always, but often, makes it difficult to make a truly strong substantiation argument.
And thus, the nuances and grey areas that come with the territory of claim substantiation. The question always is, “Is this group of studies enough to make a case?” and the answer always is: case by case. It is NOT based purely on having a type or number of studies in hand. It is also not (in isolation) a question of, “Do I or don’t I need an RCT (or another RCT)?” And it is definitely not, “Well, now that two RCTs got struck down, isn’t thus-and-such kind of study fine?”
No, the questions run more along these lines: What does the totality of the science tell us, and how strong is it? Are there gaps that need to be filled to shore up a mediocre level of evidence before I can go out with my claim? What kinds of studies can fill them, and what is the cost-benefit analysis of me doing them? What level of risk is there with the current portfolio, and is it a level the company is comfortable taking on?
Totality of the evidence is a complicated picture, but it is a sure-fire way to make sure you are delivering a product that is not only regulatory-compliant, but also has been empirically shown to work.
Has this case affected the way your company ensures its claims are substantiated?