David Vs. Goliath Revisited

Examining the possibility of conducting comparator studies on nutraceutical products.

ByAnthony L. Almada, B.Sc., M. Sc.

Nutraceuticals have long been the center of vigorous criticism, denigrated for their lack of safety and efficacy and their surfeit of unsubstantiated salutary and therapeutic claims. One tactic very rarely employed is comparator studies between a nu­traceutical and an OTC or Rx drug. Such a tactic could fulfill the adage “Be careful—you may get what you wish for.”

In this column I have repeatedly sounded off on the ubiquitous practice of bioactive ingredient and nutraceutical/cosmeceutical finished goods marketers claiming to have the superior and “best” in­gre­di­ent/product, relative to their own pre­­vious iterations and, more em­phatically, to those of their competition. The norm for the natural products industry is pirated science, science on only one bioactive (of a multi-ingredient product) and/or an anemic attempt at science after sales. Arguably, many nutraceutical products are embraced and adopted by consumers because they promise a “natural, drug-free” solution to a condition (undesirable blood lipid profile), lifestyle objective (photoaging/wrinkles) or even a disease (obesity, diabetes). Case in point: for many of those living with osteo­arthritis or chronic, undiagnosed joint pain, reaching for a bottle of chondroitin and/or glucosamine sulfate is equally or more frequent than reaching for an NSAID like Advil® or Vioxx®. Indeed, the use of such a nutraceutical may reduce the frequency of use of acute pain relieving/anti-inflammatory drugs.

Using the previous example, the nutraceutical is no different from an OTC/Rx drug except that it is governed by a different set of rules and the active ingredient(s) occur in, are derived from or are chemically identical to Mother Nature’s tool box (we’ll set aside GMPs and shelf stability for this exercise). With so much confidence bestowed upon OTC and Rx drugs why not assess how natural products would fare in mano a mano comparisons?

The natural products industry’s past experience in this realm has been both devastating and delightful. The April 2002 ill-fated Zoloft® (sertraline) versus Lichtwer Pharma St. John’s Wort (SJW) extract study in JAMA opened up a hole for Hypericum products to fall into and inserted one more nail into the herbal products coffin. Oral beta-carotene supplements failed to prevent the development of solar keratoses in a susceptible population, while a water resistant sunscreen (an OTC drug) was effective (Arch Dermatol, 2003). In contradistinction (yet during the hockey stick growth curve of botanicals), a comparator study between Proscar® (finasteride) and Permixon® (Pierre Fabre innovator saw palmetto extract) in men with benign prostatic hyperplasia found the two to be efficacy-equivalent (Prostate, 1996). This large, multinational 26-week study became one of the cornerstone studies that fostered a similar conclusion in a systematic review of saw palmetto in BPH, which appeared in a special issue of JAMA in 1998 and in a 2002 Cochrane Database Review.

From a proprietary positioning perspective a modest-sized randomized clinical trial with an active control (read an OTC or Rx drug of choice for the indication), with or without a placebo control group, compared to a competitively insulated nutraceutical or cosmeceutical, could serve up a seemingly invincible suite of outcomes (assuming the latter product performs nearly as well, equally as well or superior to the active control). Flip the Zoloft vs. SJW study around to be an industry-sponsored study attempting to show pharmacoequivalence of the botanical to the Rx drug. The primary outcome measure showed both to be no better than placebo but the headlines could read (achieved through either presentation of the data at a biomedical research meeting and/or publication in a reviewed journal, and some savvy PR tactics) “Leading anti-de­pressant offers no more hope than herbal supplement.” Weaving in the side ef­fects/adverse events data from a comparator trial could foster a different headline: “Prostate drug’s appeal shrinks compared to herbal alternative.”

Such media pick-up seems unattainable, a blue sky wish. Granted, such pick-up would likely not manifest on page 1A of the New York Times or USA Today but it could in regional dailies, high circulation consumer monthlies like Prevention, SELF or Men’s Fitness and local network and national cable T.V. Even big health websites like WebMD and CBS HealthWatch or on air broadcasts like National Public Radio or CBS radio (regional or national) are feasible. A strategic, science-driven decision to stir and provoke, while infecting consumer’s with a novel story line—comparable to a well known drug—could instill that elusive and rare bioactive ingredient that is so deficient: confidence. David may not slay Goliath but many of the giant’s followers may not heed his command the next time it is uttered.NW