Opinion ID: 2775066
Heading Depth: 3
Heading Rank: 1

Heading: POM sponsored a number of studies examining the

Text: capacity of its products to improve cardiovascular health. One such study, led by Dr. Michael Aviram of the TechnionIsrael Institute of Technology, examined the effect of pomegranate juice consumption by patients with carotid artery stenosis. Carotid artery stenosis is the narrowing of the arteries that supply oxygenated blood to the brain, usually caused by a buildup of plaque inside the arteries. In Dr. Aviram’s study, ten patients with carotid artery stenosis consumed concentrated pomegranate juice daily for a 5 year, while nine patients with carotid artery stenosis served as a control group and consumed no pomegranate juice. The investigators measured the change in the patients’ carotid intima-media thickness (CIMT), an indicator of plaque buildup. They found that patients who consumed pomegranate juice every day experienced a reduction in CIMT of “up to 30%” after one year, while CIMT for patients in the control group increased by 9% after one year. POM Wonderful LLC, No. 9344, Initial Decision of ALJ at 115 ¶ 791 (U.S. Fed. Trade Comm’n May 17, 2012) (ALJ Initial Decision). As one of POM’s experts would later testify, the Aviram study, while “suggest[ing] a benefit” from pomegranate juice consumption for patients with carotid artery stenosis, was “not at all conclusive,” in part because of the study’s small sample size. Id. at 118 ¶ 802 (quoting expert testimony). In 2004, the journal Clinical Nutrition published the study. See M. Aviram et al., Pomegranate Juice Consumption for 3 Years by Patients with Carotid Artery Stenosis Reduces Common Carotid Intima-Media Thickness, Blood Pressure and LDL Oxidation, 23 Clinical Nutrition 423 (2004). Subsequently, in 2005, a larger study, led by Dr. Dean Ornish of the University of California, San Francisco and the Preventative Medicine Research Institute, followed seventythree patients with at least one cardiovascular risk factor for one year. The patients were randomly assigned either to drink one cup of pomegranate juice daily or to drink a placebo beverage. At the end of the study, Dr. Ornish and his coinvestigators found no statistically significant difference between the treatment group and the placebo group in CIMT change or any other heart-related measure. In 2006, a third, still larger study, led by Dr. Michael Davidson of the University of Chicago, followed 289 patients 6 with one or more coronary heart disease risk factors. As in the Ornish study, the patients were randomly assigned to drink either pomegranate juice or a placebo beverage each day. At the end of eighteen months, Dr. Davidson and his coinvestigators found no statistically significant difference in the rate of carotid intima-media thickening between patients in the treatment group and those in the placebo group. POM initially delayed publication of the adverse findings, but ultimately allowed publication of the study in 2009. See Michael H. Davidson et al., Effects of Consumption of Pomegranate Juice on Carotid Intima-Media Thickness in Men and Women at Moderate Risk for Coronary Heart Disease, 104 Am. J. Cardiology 936 (2009). In their final report, Dr. Davidson and his co- investigators noted that they had found some evidence of an association between pomegranate juice consumption and decreased CIMT among subgroups of patients with high triglyceride levels and low levels of HDL (“good”) cholesterol. Dr. Davidson and his co-authors emphasized, however, that the findings for those subgroups were based on “post hoc exploratory analyses” unanticipated in the study protocol. As Dr. Davidson and his co-authors noted, “post hoc exploratory analyses . . . should be interpreted with caution” because of an increased risk of “type I errors” (i.e., false positives). See id. at 941. Even for patients in the highrisk subgroups, moreover, the reduction in arterial thickness was between 4% and 9% (depending on the measurement), substantially below the 30% decrease reported by Dr. Aviram. Although Drs. Ornish and Davidson completed their arterial thickness studies in 2005 and 2006, respectively, a consumer reading POM’s promotional materials after 2006 would not have known of those studies or that they cast doubt on Dr. Aviram’s prior findings. In June 2007, for example, 7 POM distributed a brochure featuring a statement by Dr. Aviram that “POM Wonderful Pomegranate Juice has been proven to promote cardiovascular health,” along with a description of his arterial thickness study, but with no mention of Drs. Ornish’s and Davidson’s contrary findings. POM Wonderful LLC, No. 9344, Opinion of the Commission, App. B fig.10, at 5 (U.S. Fed. Trade Comm’n Jan. 10, 2013) (FTC Op.). That same summer, POM published a newsletter in which it asserted that “NEW RESEARCH OFFERS FURTHER PROOF OF THE HEART-HEALTHY BENEFITS OF POM WONDERFUL JUICE.” Id. App. B fig.16, at 3. The newsletter claimed a “30% DECREASE IN ARTERIAL PLAQUE” on the basis of Dr. Aviram’s limited study but again omitted any mention of the Ornish and Davidson findings. Id. And in 2008 and 2009, POM conducted a $1 million promotional campaign, with seventy ads in newspapers and magazines across the country, in which it trumpeted Dr. Aviram’s findings—including the 30% figure—without any acknowledgement of the contrary Ornish and Davidson studies. Id. App. B fig.25; see also id. App. B fig.19. Dr. Ornish also conducted a separate study examining the relationship between pomegranate juice and blood flow. The study followed forty-five patients with coronary heart disease and myocardial ischemia (insufficient blood flow to the heart due to narrowing of the arteries). The patients were randomly assigned to drink either pomegranate juice or a placebo beverage daily. Dr. Ornish later testified that, although his protocol called for a twelve-month study, he terminated the study abruptly after three months because the Resnicks did not follow through on their previous commitment to fund a twelve-month trial. 8 At the end of three months, patients in the treatment group outperformed patients in the placebo group on one measure of blood flow to the heart, known as the “summed difference score.” The study, however, found no statistically significant difference between the treatment and control groups on two other measures of blood flow (the “summed rest score” and the “summed stress score”), nor did it find any statistically significant differences in blood pressure, cholesterol, or triglycerides. Medical experts later noted a number of shortcomings of the study, including that patients in the placebo group began the study with significantly worse blood flow than patients in the treatment group, potentially skewing the outcomes. POM touted the results of the second Ornish study in its ads and promotional materials without noting the study’s limitations or acknowledging that patients in the treatment group showed no statistically significant improvement in blood flow on two of three measures. In September 2005, for instance, POM issued a press release announcing the study in which it asserted that “blood flow to the heart improved approximately 17% in the pomegranate juice group” and that differences in blood flow between the two groups were “statistically significant.” Id. App. B fig.8. POM continued to make similar statements in its promotional materials through 2009. See id. App. B fig.10, at 5 (June 2007 brochure claiming that “[p]atients who consumed 8oz of POM Wonderful 100% Pomegranate Juice daily for three months experienced a 17% improvement in blood flow”); id. App. B fig.16, at 3 (summer 2007 newsletter claiming “17% IMPROVED BLOOD FLOW”); id. App. B figs.37, 38, 39 (similar claims on POM websites in 2009). 2. In addition to the cardiovascular studies, petitioners sponsored research on the effect of pomegranate juice 9 consumption in prostate cancer patients. One study, led by Dr. Allan Pantuck of the University of California, Los Angeles Medical School, followed forty-six patients who had been diagnosed with prostate cancer. All of the patients had already been treated by radical prostatectomy, radiation therapy, or cryotherapy. The study called for them to drink eight ounces of pomegranate juice daily. There was no control group. The study concluded that the patients’ “PSA doubling time,” a measure of the rapidity of growth in prostate tumor cells, increased from fifteen months at the beginning of the study to fifty-four months at the end. But as Dr. Pantuck himself noted, patients who have undergone radical prostatectomy or radiation therapy for prostate cancer commonly experience a lengthening in PSA doubling time regardless of whether they consume pomegranate juice. POM, however, made no mention of the limitations of the Pantuck study in its public statements. In a July 2006 press release, POM claimed that “drinking 8 ounces of POM Wonderful pomegranate juice daily prolonged post-prostate surgery PSA doubling time from 15 to 54 months,” without noting that some or all of the increase in the patients’ PSA doubling times may have resulted from the radical prostatectomies or radiation treatments undergone by the patients. Id. App. B fig.9, at 2. POM advanced similar claims in a June 2007 brochure and in a fall 2007 newsletter, again with no disclosure of the study’s limitations. See id. App. B figs.10, 17. In 2008 and 2009, POM ads in the New York Times Magazine and TIME Magazine asserted that prostate cancer patients who drank eight ounces of POM Wonderful 100% Pomegranate Juice a day for at least two years experienced “significantly slower” PSA doubling times, once again without any acknowledgment that the patients’ PSA doubling times may have slowed regardless of whether they consumed pomegranate juice. Id. App. B figs.21, 27; see also 10 id. figs.36, 37, 38, 39 (similar claims on POM websites in 2009). 3. Petitioners additionally sponsored research of the effects of pomegranate juice consumption in men with mild to moderate erectile dysfunction. One study, led by Dr. Harin Padma-Nathan, a urologist in Beverly Hills, California, followed fifty-three patients over eight weeks. The study used a “crossover” design: one group of patients consumed pomegranate juice for the first four weeks and then consumed a placebo beverage for the next four, while a second group consumed the placebo beverage for the first four weeks and pomegranate juice for the next four. Dr. Padma-Nathan and co-investigators evaluated the results using two measures: the International Index of Erectile Function (IIEF), a fifteenquestion instrument, and the Global Assessment Questionnaire (GAQ), a one-question test. The IIEF is a “validated” tool, which means that the measure has been shown to have statistical reliability, while the one-question GAQ is not a validated measure for assessing erectile function. See generally R. C. Rosen et al., The International Index of Erectile Function (IIEF): A State-of-the-Science Review, 14 Int’l J. Impotence Res. 226, 226 (2002). Dr. Padma-Nathan’s study showed some evidence that patients scored higher on the GAQ measure after drinking pomegranate juice. But the p-value—the probability of observing at least as strong an association between pomegranate juice consumption and GAQ scores due to random chance—was 0.058, falling just short of statistical significance at the conventional p<0.05 level. On the scientifically validated IIEF measure, however, the difference between patients’ scores after drinking pomegranate juice and after drinking the placebo beverage came nowhere near statistical significance: there was nearly a 3/4 likelihood of 11 observing as strong an association due to random chance (p=0.72). See C.P. Forest, H. Padma-Nathan & H.R. Liker, Efficacy and Safety of Pomegranate Juice on Improvement of Erectile Dysfunction in Male Patients with Mild to Moderate Erectile Dysfunction: A Randomized, Placebo-Controlled, Double-Blind, Crossover Study, 19 Int’l J. Impotence Res. 564, 566 (2007). In its public statements about Dr. Padma-Nathan’s study, POM made no mention of the negative results with respect to the validated IIEF measure. POM instead touted the study outcomes based exclusively on the non-validated GAQ measure. A 2007 POM press release thus described Dr. Padma-Nathan’s study as follows: At the end of . . . each four week period, efficacy was assessed using the International Index of Erectile Function (IIEF) and Global Assessment Questionnaire (GAQ). The IIEF is a validated questionnaire that has been demonstrated to correlate with ED intensity. The GAQ elicits the patient’s self-evaluation of the study beverages’ effect on erectile activity. Forty seven percent of the subjects reported that their erections improved with POM Wonderful Pomegranate Juice, while only 32% reported improved erections with the placebo (p=0.058). FTC Op. App. B fig.15, at 2. That press release, while referencing IIEF and thus suggesting that its description of the findings would account for that measure, in fact promoted the results based solely on the GAQ measure with no acknowledgment of the adverse findings on IIEF scores. In 2009 and 2010, POM similarly touted the GAQ findings— 12 again without any mention of the negative IIEF results—on websites and in print ads. See id. App. B figs.33, 36, 37, 38, 39.